Ed Friedlander, M.D., Pathologist

Presentation: The patient with something subtle that you DON'T want to overlook
Title:        Pituitary
Date & Time:  Friday, January 22, 2010 at 10 AM
Lecturer:     Ed Friedlander MD

Endocrine Pathology
Path photos with labels
Ohio State

Photo Library of Pathology
U. of Tokushima

Iowa Virtual Microscopy
Have fun

Utah cases for path students
Juliana Szakacs MD

Tulane Pathology Course
Great for this unit
Exact links are always changing

Endocrine System
Great pathology images
Indiana Med School

Endocrine Pathology
Virginia Commonwealth U.
Great pictures

Brown Digital Pathology
Some nice cases

Photos, explanations, and quiz
Indiana U.

Taiwanese pathology site
Good place to go to practice

Normal pituitary

WebPath Photo

Normal pituitary

WebPath Photo

Pituitary gland
Pars intermedia

{14945} anterior (A) and posterior (B) pituitary
{02294} anterior pituitary, histology; curious stain, don't worry about the colors
{14948} posterior pituitary, histology (arrow: Herring body)

Normal anterior pituitary

WebPath Photo

Normal posterior pituitary

WebPath Photo





ANTERIOR LOBE ADENOMAS (NEJM 324: 822, 1991; curious five-tier WHO classification Cancer 78: 502, 1996; tumorigenesis J. Clin. Inv. 112: 1603, 2003)

{15683} pituitary adenoma, gross
{15682} pituitary adenoma with hemorrhage
{49422} pituitary adenoma, gross
{49612} pituitary adenoma, gross
{09214} pituitary adenoma, histology (this was a prolactinoma; you couldn't tell)
{24821} pituitary acidophilic adenoma, Orange G stain (acromegaly)
{09215} pituitary adenoma, histology
{15679} pituitary adenoma, histology
{05026} pituitary adenoma, x-ray
{00344} pituitary adenoma, x-ray

Pituitary adenoma
Pittsburgh Pathology Cases

Pituitary adenoma
Pittsburgh Pathology Cases

Pituitary adenoma
WebPath Case of the Week

Pituitary microadenoma

WebPath Photo

Pituitary adenoma

WebPath Photo

{49419} giant and her sisters
{16101} acromegaly
{25668} acromegaly (which twin has it?)
{49421} acromegaly, hand (compared with normal)

      Excess growth hormone before puberty produces excessively tall stature. In the past, these people typically were crippled by nerve, muscle, and joint problems, acquired acromegalic features as they got older, and died young of complications of their diabetes.

        A giant is defined to be a human over seven feet tall (you may hear 200 cm instead).

Gheorge Muresan
George Muresan

      Excess growth hormone after puberty produces acromegaly.

        The typical acromegalic has a huge jaw ("prognathism"), huge brows, huge tongue, and huge hands (with "spade fingers"), develops a deep guttural voice, gets an oily skin (extra sebaceous glands), gets joint deformities (if not frank arthritis), and suffers from secondary diabetes and often sleep apnea.

          The popular wisdom is that acromegalics are around 2.5 x more likely to develop tumors (benign, malignant) than their counterparts (Arch. Int. Med. 151: 1629, 1991). Lately this hasn't held up (J. Clin. Endo. Metab. 85: 3417, 2000).

          Acromegaly kills its victims, taking an average of 10 years off life. Effective treatment of the adenomas brings overall mortality back to levels similar to the unaffected (J. Clin. End. Metab. 83: 3409, 1998).

          * Growth hormone is of course popular among bodybuilders and "anti-aging" cultists, who obtain it though it is not medically indicated (JAMA 299: 2792, 2008 reviews the genuine indications -- adult growth hormone deficiency needs a proper workup; JAMA now suggests stimualtion testing and a hGH level).

        * Andre "the Giant" Rousimoff, the famous wrestler, had acromegaly; he was 7'4" tall and weighed 520 lb when he died at age 46. Several movie villains have been played by acromegalics. My favorite is Richard Kiel as "Jaws" from "Moonraker". Acromegalic Rondo Hatton (here or here, from the 1940's B-movies, "could have played Frankenstein without make-up". Dalip Singh evidently has gigantism-acromegaly; he remains very physically fit.

        The lab workup of acromegaly is straightforward. Your screening test is a spot blood insulin-like growth factor I (IGF-I). If this is normal, you have ruled out acromegaly. Next, attempt suppression of the hGH levels to <1 microgram/L by administering 75 mg of glucose orally (yuck). If this fails, your patient probably has acromegaly.


      Most pituitary giants and acromegalic patients have a pituitary macro-adenoma (i.e., >10 mm). The best treatment is still surgical removal of this adenoma, though some inoperable patients get fair results with the somatostatin analog octreotide (J. Clin. End. Metab. 87: 4554, 2002; update J. Clin. Endo. Metab. 90: 1856, 2005, also J. Clin. Endo. Metab. 91: 1397, 2006).

        * There's a growth hormone receptor antagonist called pegvisomant available that seems to work for youngsters from whom the adenoma cannot be fully removed (J. Clin. Endo. Metab. 93: 2953, 2008).

        The classic "acidophilic adenomas" are "densely granulated", which gives a better surgical prognosis. Many of these patients have "sparsely granulated / chromophobe" adenomas instead. There's no correlation between growth hormone levels and tumor type; which type responds best to which medical therapies is presently under study.

        The big news in pituitary disease during the last few years has been the application of the long-acting somatostatin analogue octreotide ("Sandostatin") to the treatment of acromegaly. This often shrinks the tumor, and seems to make these tumors physically softer, making it easier to remove them surgically (J. Clin. End. Metab. 86: 2779 & 5194, 2001, J. Clin. Endo. Metab. 90: 440 & 1588, 2005; lots more). A long-acting depot form is available.

        Radiation is reserved for those who have failure with surgery (J. Clin. Endo. Metab. 88: 3105, 2003).

      Not surprisingly, the new transgenic mice that overproduce human growth-hormone releasing factor get hyperplasia and adenomas of growth hormone and prolactin producing cells (Endocrinology 131: 2083, 1992), and morphologic changes elsewhere resembling those in acromegaly (Am. J. Path. 141: 895, 1992).

      * There are a couple of poorly-understood "acromegaloid" syndromes, with the acromegaly look and the insulin resistance, but normal growth hormone levels. Some of these folks have elevated levels of other growth factors. There is also a familial tumor syndrome, 11q13, the gene not yet cloned, which produces only GH-omas (J. Clin. Endo. Metab. 86: 542, 2001; gene still not isolated J. Clin. Endo. Metab. 90: 6580, 2005).


{09367} Cushingism
{09368} Cushingism
{09369} Cushingism
{09370} Cushingism
{16110} Cushingism
{16111} Cushingism
{49427} Cushingism
{25669} Cushingism, before and after treatment

      You are already acquainted with the signs of Cushingism. "Cushing's disease" implies production of ACTH by a pituitary tumor, usually a small microadenomas. There is usually not enough ACTH production to darken the skin.

        While the role of CRF in producing these adenomas may be important, they do appear to be monoclonal overgrowths (J. Clin. End. Met. 75: 472, 1992) that have lost some, but not all, of the ability of high levels of cortisol to inhibit their growth (Endo. Rev. 20: 136, 1999).

        * One famous fact about these microadenomas is that they're so small and mushy that they are likely to wash out before the surgeon is even able to find them. The ACTH levels drop after surgery, though, letting everyone know what's happened.

        * Transgenic mice (two kinds) with Cushing's disease: Am. J. Path. 140: 1071, 1992.

      As you know, most cases of "idiopathic adrenal hyperplasia" were really due to ACTH-omas. In the old days when we'd remove both hyperplastic adrenals, the ACTH-oma, which was under some feedback inhibition, would grow to a tremendous size, turn the patient's skin brown, and blind and kill the patient ("Nelson's syndrome"). Establish your diagnosis and take the pituitary out instead.

        Back in the Bad Old Days, if you got an ACTH-producing pituitary adenoma, you would probably be really sick for a while and then die of it. Today you will probably get a cure (Ann. Int. Med. 130: 821, 1999); however persistence / recurrence is disturbingly common (J. Clin. Endo. Metab. 89: 6348, 2004).

        * Future catheter artists: Even today, it's often hard to find the adenoma on imaging studies, especially in younger folks (J. Clin. Endo. Metab. 90: 5134, 2005). It's long been a practice to find and lateralize non-visualized adenomas by comparing simultaneous ACTH measurements in the petrosal sinuses (see, for example, Am. J. Ob. Gyn. 171: 563, 1994). This is being applied to more diseases (Am. J. Med. 87: 679, 1989; NEJM 324: 822, 1991).


      Mysteriously (and fortunately), TSH-producing adenomas of the pituitary gland are quite rare. They tend to look a little bit anaplastic and to be locally aggressive.

      "Pituitary hyperplasia due to resistance to thyroid hormone" (J. Clin. End. Met. 75: 1071, 1992) isn't well-understood. Patients have excess hTSH and become hyperthyroid.

    * Future pathologists:

      INCIDENTALOMAS: It's been known for decades that in maybe 30% autopsies on grown-ups, if you look really hard, you'll find a "pituitary microadenoma", generally "prolactin-producing". (One recent series of old autopsy pituitaries, without a diligent search of each, found 10% with 1 "adenoma", 1% with 2 or more: J. Neurosurg. 74: 243, 1991; we're now using our high-resolution MRI's to find that around 10% of live folks have them, too: Ann. Int. Med. 120: 817, 1994; Cancer 101: 613, 2004). Just how "autonomous" these "tumors" are, and their real status as "neoplasms", is very dubious; the one's I've seen look like typical endocrine-gland hyperplastic nodules ("gland bumps"). Nowadays they're routinely called "incidentalomas"; if there are no hormonal abnormalities, leave them alone, even if the pituitary seems a bit large (J. Clin. Endo. Metab. 86: 3009, 2001).

        Clinicians are now picking these up on NMR scans and learning to ignore them, except for the rare ones over 10 mm (Ann. Int. Med. 122: 925, 1990; Arch. Int. Med. 155: 181, 1995).

        Sometimes telling microadenoma from normal gland or hyperplastic is tricky. Microadenomas will lack the normal reticulin pattern of pituitary gland, and have homogeneous cells (morphology, immunostaining). Hyperplastic glands retain normal reticulin but the cell groups are larger.

      Occasionally, secondary prolactin production is caused by the tumor blocking the portal system, keeping dopamine from reaching the non-neoplastic gland.

      Most of the pituitary hormones can be secreted by carcinoids and oat-cell carcinomas elsewhere in the body.

      Some pituitary adenomas are eosinophilic not because they derive from GH- or prolactin-producing cells, but because they are packed with mitochondria. You've seen these "oncocytomas" or "Hürthle cell adenomas" elsewhere.

      Nowadays, some pathologists diagnose ATYPICAL PITUITARY ADENOMA when the Ki-67/MIB-1 labeling exceeds 3% and the nuclei stain with p53. They're much more likely to recur, but really aren't cancer.

      Pituitary carcinomas are very rare, and no one knows exactly how to distinguish them from adenomas. So far, what has been most helpful is immunostaining for Ki-67 and p53 (J. Clin. Endo. Metab. 90: 3089, 2005).

Pituitary adenoma
Pittsburgh Illustrated Case


    The symptoms of panhypopituitarism are highly variable.

      Growth hormone doesn't have spectacular effects on adults, and for years, we taught that its impact is negligible. Now we know this isn't true. It slows the body wasting that occurs in old age (NEJM 323: 1, 1990). Adults lacking growth hormone have more fat and less muscle per pound of body weight (Am. J. Clin. Nutr. 55: 918, 1992); the heart may also actually be weaker (Br. Heart. J. 67: 92, 1992), and growth hormone also helps maintain the skeletal muscles. See below.

      Loss of gonadotropins produce loss of libido and body hair.

        * There's an idiopathic, adult-onset loss of gonadotropin that produces treatable male infertility NEJM 336: 410, 1997.

      Loss of prolactin prevents lactation, which would only be noticed after childbirth.

      Loss of thyrotropin produces secondary hypothyroidism (i.e., cretinism in children, problems culminating in myxedema in adults).

      Loss of ACTH produces secondary adrenal insufficiency, which is just as deadly as primary adrenal insufficiency. (Fortunately, this happens only very late in the progression of the disease.)

      If the posterior pituitary gland is involved, loss of ADH produces pituitary diabetes insipidus.

      Patients with hypopituitarism from a variety of causes are unusually prone to precocious atherosclerosis. The premature cardiovascular disease mortality has been known for decades (Lancet 336: 285, 1990). One robust finding is that "adult-onset growth hormone deficiency" (see below) is a risk factor for atherosclerosis, and now it appears that replacing it helps prevent / reverse the process (J. Clin. Endo. Metab. 93: 3416, 2008).

    Most of the time, hypopituitarism is due to

      (1) destruction of the pituitary by a pituitary adenoma, surgery, radiation (Q. J. Med. 70: 145, 1989), or trauma;

      (2) Sheehan's pituitary necrosis, or

      (3) the "empty sella syndrome".

      Also worth considering are vascular problems (i.e., cavernous sinus thrombosis, obvious) and sarcoidosis (not at all obvious).

      LYMPHOCYTIC HYPOPHYSITIS is a rare cause of pituitary insufficiency and a mass lesion; the traditional teaching is that most patients are postpartum women but more recently sex ratios have been about equal (J. Neurosurg. 101: 262, 2004). As a cause of sudden death: AMFJP 30: 61, 2009. GRANULOMATOUS HYPOPHYSITIS produces a mass and sometimes pituitary insufficiency: J. Neurosurg. 71: 681, 1999; I've seen a case. Both are likely to be be operated as "adenomas" and the correct diagnosis established later by the pathologist; one must be extremely alert to suspect the diagnosis before the (? unnecessary) surgery (J. Clin. Endo. Metab. 86: 1048, 2001). For some reason, the disseminated histiocytic diseases (Langerhans cell histiocytosis, Erdheim-Chester, Rosai-Dorfman) are prone to attack the adenohypophysis as well.

      Some grown men with "idiopathic hypogonadotropic hypogonadism" have autoantibodies against the gonadotropin secreting cells of the pituitary (J. Clin. Endo. Metab. 92: 604, 2007).

      * A genetic syndrome lacks a transcription factor needed for making growth-hormone, prolactin, and TSH (Science 257: 1118, 1992.)

      * Yet another mutation, lack of PROP1, prevents production of all the hormones of the adenohypophysis except for (sometimes) ACTH (Nat. Genet. 18: 147, 1998; J. Clin. Endo. Metab. 85: 4566, 2000; J. Clin. Endo. Metab. 89: 5256, 2004). POU1F prevents productions of GH, prolactin, and TSH (J. Clin. Endo. Metab. 90: 4762, 2005). Even ACTH usually is insufficient: J. Clin. Endo. Metab. 89: 5256, 2004.

      Hypopituitarism after TB meningitis in childhood is a problem in the poor nations (Ann. Int. Med. 118: 701, 1993). In this series, around 1/5 of childhood survivors of TB meningitis were left with hypopituitarism.

      SHEEHAN'S PITUITARY NECROSIS ("postpartum pituitary necrosis") occurs when shock complicates a problem delivery. The drop in blood pressure results in inadequate blood supply to the gland, which is already hyperplastic and has its vessels squeezed half-shut. Hence, it undergoes watershed infarction.

        Less often, pituitary necrosis results from sickle cell disease, temporal arteritis, or trauma.

        * For some reason, diabetics are prone to hemorrhages and necrosis in the pituitary. This may even help the diabetic state.

        Usually the gonadotropins and prolactin are the most decreased. The typical Sheehan's patient fails to lactate or resume menstruating after delivery. When necrosis is less complete, the disease tends to progress "as the remaining cells are entrapped in scar tissue" (more likely, the scar diverts blood from the good gland).

      The EMPTY SELLA SYNDROME classically results from slow crushing of the gland by CSF pressure when the hole in the diaphragma sellae is wide enough (or there is another defect) to allow arachnoid to herniate into the sella (most common).

        Recent work confirms the traditional wisdom that "empty sella" usually results from increased intracerebral pressure (J. Neurosurg. 103: 831, 2005). Oh... the authors also remind referring physicians how embarrassing it is to miss CSF rhinorrhea as the cause.

        Some of these patients develop pituitary insufficiency.

        Future radiologists: Other reasons to have an empty sella include old Sheehan's, or total necrosis of an old adenoma, or previous surgery. Again, many of these patients have hypopituitarism of one kind or another.

    The older medical literature is full of descriptions of extreme weight loss in end-stage hypopituitarism ("Simmonds's cachexia"). These must be the patients who finally lose ACTH (often the last to go).


    Failure to produce normal amounts of growth hormone in childhood results in miniature, well-proportioned people. Causes range from "idiopathic" to various genetic syndromes to other causes of hypopituitarism.

      Around 50% of "idiopathic dwarves" are breech or transverse deliveries, and the damage to the hypothalamic-pituitary axis may occur when their little skulls get crunched: Lancet 338: 480, 1991

      After traumatic brain injury, there is often considerable loss of growth hormone (Arch. Phys. Med. 86: 463, 2005). New studies of professional and elite amateur boxers show that growth hormone and ACTH are often impaired -- watch this one (Ann. Int. Med. 148: 827, 2008.)

      Laron dwarves (short, frontal bossing; the defect is in the growth hormone receptors; update J. Clin. Endo. 83: 4481, 1998).

      Quite a few adults who are "just short" turn out to have marginal ability to make growth hormone, and they seem to benefit from replacement (J. Clin. Endo. Metab. 89: 1586, 2004).

      Pygmies also have tissues that do not respond well to growth hormone; apparently in Africa and the Philippines there is a relative deficiency of the growth hormone receptor ("pituitary dwarfism type II"; J. Ped. Endo. 15: 269, 2002; Clin. Endo. 51: 741, 1999).

      "Get Shorty!" Now it turns out that a lot of just-plain-short people have minor defects in their growth hormone receptors: NEJM 333: 1093, 1995.

    If thyrotropin is normal or thyroid hormone is replaced, the children will be of normal intelligence. If gonadotropin production is normal or sex steroids are administered, puberty should occur normally. And please don't miss adrenal insufficiency in these kids; they continue to die of sudden adrenal crisis in disturbingly large numbers.... (J. Clin. End. Metab. 81: 1693, 1996).

    And of course, we used to donate autopsy pituitaries to make growth hormone to help these kids attain normal height. (* Regrettably, a significant amount of this precious substance ended up at the gym instead, as part of quack "muscle building" schemes.) Now we have recombinant hGH.

    NOTE: Before you diagnose an endocrine problem, remember that mysterious "failure to grow" can and does result from lack of parental warmth and emotional nurturing. This is more common than endocrine dwarfism.

    ADULT GROWTH HORMONE DEFICIENCY, unheard-of a few years ago, is now being diagnosed both in patients who've had previous pituitary surgery or tumors, and in people who seem to waste their lean tissues and simply do not feel or perform well. The screening test is IGF-I, which should be low for age-and-sex-matched controls. The patients report a spectacular improvement in sense of well-being upon hormone replacement (Clin. Endo. 54: 709, 2001). Especially, suspect it when the voice starts getting higher and raspier (J. Clin. Endo. Metab. 90: 4128, 2005). As noted above, the increased atherosclerosis risk seems reversible with replacement. Exactly how common this really is gets widely debated -- the real question is, "Who's likely to benefit from the expensive replacement therapy?"

CRANIOPHARYNGIOMA ("adamantinoma", "ameloblastoma", both named for tooth enamel)

{15685} craniopharyngioma, gross
{15686} craniopharyngioma, gross
{15687} craniopharyngioma, histology
{15688} craniopharyngioma, histology


KU Collection

Notice the benign squamous pearl
KU Collection


WebPath Photo

    This is a benign tumor of Rathke's pouch remnants that generally occurs just above the pituitary and sella turcica. It is locally aggressive but does not metastasize (* like the closely-related ameloblastoma of the jaw). The optic nerves and chiasm, and then the hypothalamus, are damaged.

    Most patients are under twenty, but no age is immune. Little is known of the etiology or genetics (J. Neurosurg. 98: 162, 2003).

    Grossly, most of these tumors usually filled with little cysts that contain an unsavory, cholesterol-rich fluid ("machine oil").

    Microscopically, the tumor usually recalls developing tooth enamel ("adamantinomatous type"), with areas of columnar cells, stellate mesenchyme, usually calcification, sometimes stratified squamous stuff and/or bone.

      * Future pathologists: You can tell a adamantinomatous craniopharyngioma from an innocent Rathke cyst because the craniopharyngioma exhibits nuclear staining with beta-catenin.

      A minority of craniopharyngiomas exhibit simple squamous epithelium and fibrous cores ("papillary growth pattern") instead.

    The mainstay of craniopharyngioma treatment is surgery (series with pretty good results 97: 3, 2002), but intratumoral injection of bleomycin is a possibility for poor-surgical risk cases: J. Neurosurg. 84: 124, 1996.

    Future pathologists: The papillary variant mostly occurs in adults, and is less aggressive (J. Neurosurg. 83: 206, 1995). RATHKE'S CLEFT CYSTS of the pars intermedia, a common tiny incidental autopsy finding, may sometimes be large enough to be seen in life; must be distinguished from craniopharyngiomas. These cysts can compromise eyesight, too (Am. J. Ophth. 119: 86, 1995; J. Neurosurg. 102: 189, 2005). Very rarely, a squamous cell carcinoma arises in a craniopharyngioma (Arch. Path. Lab. Med. 124: 1356, 2000).

DIABETES INSIPIDUS (Am. Fam. Phys. 55: 2146, 1997; Arch. Int. Med. 157: 1293, 1997).

    Because the posterior pituitary gland is really processes of hypothalamic neurons, a variety of processes can damage it. Remember:

      Causes within the sella

      • compression by pituitary adenoma -- this is uncommon even if a symptomatic adenoma is present
      • pituitary infarction from any cause
      • pituitary ablation (surgical, radiation)
      • sarcoidosis
      • mutant ADH (autosomal dominant, J. Clin. Inv. 99: 1897, 1997; J. Clin. End. Metab. 81: 192 & 1787, 1996; J. Clin. Endo. Metab. 84: 3351, 1999)

      Causes above the sella

      • old bacterial meningitis
      • damage from encephalitis
      • meningeal tuberculosis
      • hypophyseal glioma or germinoma
      • craniopharyngioma
      • metastatic cancer
      • skull trauma

      Also remember nephrogenic diabetes insipidus, the inability of the kidney to respond to ADH (mutant ADH receptor: Nature 359: 235, 1992; also other medullary diseases and lithium therapy).

      * Dr. Roy Meadow again: Your lecturer believes that the (overzealous and now-disgraced) "discoverer of Munchausen's by proxy" was correct in recognizing salt poisoning as a means of making children sick (Arch. Dis. Child. 68: 448, 1993). However, remember that plenty of kids have diabetes insipidus and even more have simply dehydration.

    * There are two posterior pituitary gland tumors.

      PITUICYTOMAS are astrocytomas arising from the pituitcytes. I've never seen one.

      The GRANULAR CELL TUMOR resembles similar tumors of Schwann cell origin seen elsewhere (but see Virch. Arch. B., 60: 413, 1991). Think of McCune-Albright.


    Patients have continual ADH production no matter what the current plasma osmolality. Water leaks back freely from the collecting ducts, the blood becomes hypotonic, and the patient loses the ability to produce dilute urine.

      Low blood tonicity leads to seizures and then to death. Correct it too fast by pushing in sodium, and your patient develops central pontine myelinolysis. Be sure you know what you're doing.

    The syndrome, when really present, is almost always due to ectopic ADH production by a tumor (typically, oat cell carcinoma; occasionally a carcinoid, * thymoma, or * lymphoma; rarely, widespread pulmonary TB produces excess ADH for some reason, and the last one to remember is acute intermittent porphyria and its variants). Pituitary problems almost never produce inappropriate ADH.

    The best treatment is to make the "inappropriate ADH" appropriate by restricting water.

      Before you wrongly diagnose "syndrome of inappropriate ADH" in your cachectic, hyponatremic cancer patient, remember that generalized body protein depletion re-sets the "osmostat", and hyponatremia is usual and normal. Don't add to your patient's discomfort by foolishly denying him or her access to the water pitcher.

    There is no known oxytocin-excess or deficiency syndrome.


    These result from abnormal function of the hypothalamus, reflected in problems with sexual development.

    FROEHLICH'S SYNDROME is hypothalamic hypogonadism plus obesity. Affected boys are obese (i.e., have increased appetite), show a female pattern of fat distribution, and have delayed (if ever) appearance of primary or secondary sex characteristics.

      The problem in "adiposogenital dystrophy" may be in the hypothalamus (true Froehlich's -- these kids may or may not be retarded; do you think emotions could be the cause?). It can equally well be due to hypopituitarism from any cause in someone who like to eat. It could also be "constitutional" without a demonstrable hypothalamic lesion (the fat boy that stays child-like; you knew him).

      Good luck sorting all these out; endocrinologists use sophisticated stimulation and suppression tests. Current thinking focuses on a variety of etiologies, known and unknown, that prevent the normal pulsatile secretion of GnRH.

{49423} Froehlich's man, age twenty

    After surgery for craniopharyngioma, which often damages the hypothalamus, MRI can predict who, and will not, get morbid weight gain (J. Clin. End. Metab. 81: 2734, 1996).

    You already know PRADER-WILLI.

    * BARDET-BIEDL (used to be "Laurence-Moon-Biedl") is a hereditary complex with retinitis pigmentosa, polydactyly, and a similar picture to Froehlich's. There are at least three loci (Am. J. Hum. Genet. 72: 650, 2003).

    KALLMANN'S SYNDROME is a brain malformation with anosmia (no sense of smell) and Froehlich's. The best-known gene is KAL1, which directs neuronal migration; two other loci are known.

      * Jazz singer/musician "Little Jimmy Scott", who's delighted audiences for over half a century, has Kallmann's, which gave him his distinctive child-like appearance and voice.

      An autosomal dominant Kallman's: Nat. Genet. 33: 463, 2003.

Jimmy Scott

    * GPR54 mutations lead to no-puberty (NEJM 349: 114, 2003).

    MCCUNE-ALBRIGHT SYNDROME (often just "Albright") is a syndrome with cutaneous café-au-lait ("coffee with milk") spots (with irregular borders), polyostotic fibrous dysplasia, and precocious puberty caused (maybe sometimes) by a curious hypothalamic hamartoma that produces LH-releasing hormone. (These hamartomas are infamous for causing puberty before age 2. McCune-Albright kids also have other reasons for having hormonal problems.) Much more about McCune-Albright (a genetic disease that cannot be transmitted parent to child) when we study bone.

    * Septo-optic dysplasia, homeobox gene HESX1, multiple birth defects including several malformations of the forebrain; there are others (Nature 403: 658, 2000).

    * Update on all the genes involved in pituitary development and neoplasia: J. Clin. Inv. 112: 1603, 2003.

    I have "HPA Axis Disease!" There's considerable research interest right now in subtle physiological alterations of the hypophyseal-pituitary axis as a result of life experience and/or subtle genetic differences. This supposedly explains why some people overeat, get post-traumatic stress disorder (J. Clin. Psych. 62S17: 41, 2001), functional GI troubles (Am. J. Med. 107(5A): 12S, 1999), fibromyalgia, etc., etc. Cause or effect, the results are interesting; the axis is easy to study by stimulation and suppression tests. Respectable psychiatrists are rediscovering the dexamethasone suppression test (if abnormal, the patient is MUCH more likely to suicide: Am. J. Psych. 158: 748, 2001; circadian and day-to-day rhythms distinguish various types of severe depression Arch. Gen. Psych. 57: 755, 2000). Having been badly abused as a child seems to make a person oversecrete CRF / downregulate CRF receptors etc., etc. (Am. J. Psych. 158: 575, 2001), PTSD patients exhibit an enhanced ACTH suppression to dexamethasone (Am. J. Psych. 161: 1397, 2004), and this will make "nature vs. nurture" almost impossible to sort out for now. "HPA axis" is now becoming a "pop" diagnosis, in a class with chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities (except for the last, I think there is something real, but there are plenty of somatizers and it is hard to sort out.)


    Little pituitary INFARCTS are common in patients who die with intracranial problems.

{10747} pituitary infarct

    CROOKE'S HYALINE CHANGE is seen in ACTH-producing cells, with overly-dense cytoskeleton, sometimes with ringlike inclusions ("enigmatic bodies", giant lysosomes). It results from ACTH, when they have suffered chronic feedback suppression by circulating glucocorticoids (iatrogenic, from an autonomous adrenal adenoma, in the non-neoplastic corticortophs in Cushing's disease, etc.)

    We'll leave you to sort out the "ethical aspects" of hGH therapy. It's fascinating, and opens into area of drug-company gouging, whether feebleminded people should be treated, whether it's right to ask society to pay $300,000 per pituitary dwarf, whether Mr. Stallone and the boys raised on hGH to become taller adults (now commonplace) are right to do this, and whether we have a duty to treat an American boy who'll probably grow up to be less than 5'6", which will diminish his chances for marriage and getting a good job. (No, it's not right, but it's an ugly fact of life.)


    Endocrine disease is especially worthy of your serious attention because (1) it is prevalent; (2) it is generally very treatable; (3) if you diagnose it incorrectly, you doom the patient to lifelong medication; (4) if you miss it, you doom the patient to long-term ill health and probably "mental illness"; (5) Many (if not most) cases of endocrine disease get missed for a long, long time.

    You'll learn how to establish the presence of various endocrine syndromes and diseases while you are on Internal Medicine. Again, remember that for most suspected non-thyroid endocrine diseases, you'll need a stimulation test ("Can the patient produce the hormone in question at all?") or a suppression test ("Can we suppress production of the hormone in question as we could in a healthy patient?"). I don't want any more requests for a "random growth hormone assay" on a short kid.


{00135} thyroid, normal
{09213} pituitary, normal
{09362} thyroid scan radionucleotide, normal
{11204} adrenal and nerve, normal
{11207} adrenal and nerve, normal
{11210} adrenal and nerve, normal
{11754} thyroid, normal
{11755} thyroid, normal
{11803} thyroid, normal
{12866} sella turcica, normal anatomy
{12903} thyroid gland, normal
{12983} sella turcica, normal
{12986} sella turcica, normal
{12992} sella turcica, normal anatomy
{12995} sella turcica, normal
{12998} sella turcica, normal
{13004} sella turcica, normal
{13007} sella turcica, normal
{13010} sella turcica, normal
{13013} sella turcica, normal
{13016} sella turcica, normal
{13019} sella turcica, normal
{13022} sella turcica, normal
{13025} sella turcica, normal
{13028} sella turcica, norma
{13169} adenoma, pituitary
{14942} hypophysis, normal
{14942} hypophysis, normal
{14943} adenohypophysis (pars distalis), normal
{14943} adenohypophysis (pars distalis), normal
{14944} pituitary (anterior & posterior)
{14945} pituitary (anterior & posterior)
{14946} pituitary trabeculae, normal
{14947} neurohypophysis, normal
{14948} neurohypophysis, normal
{15034} adrenal, normal
{15035} adrenal gland (zones), normal
{15036} adrenal gland (zones), normal
{15037} adrenal gland (cortex), normal
{15038} adrenal gland (cortex), normal
{15039} adrenal gland (cortex), normal
{15040} adrenal gland (cortex), normal
{15041} adrenal gland (cortex, lipid stain)
{15042} adrenal gland (cortex, lipid stain)
{15043} adrenal gland (medulla), normal
{15044} adrenal gland (medulla), normal
{15045} adrenal gland (medulla, chromaffin stain)
{15046} adrenal gland (medulla, chromaffin stain)
{15048} thyroid gland, normal
{15049} thyroid gland, normal
{15050} thyroid inactive, normal
{15051} thyroid gland (follicle cells), normal
{15052} thyroid gland (active follicle cells)
{15053} thyroid gland (inactive follicle cells)
{15054} thyroid gland (parafollicular cells)
{15055} thyroid gland (parafollicular cells)
{15056} parathyroid gland fetal, normal
{15057} parathyroid gland, normal
{15058} parathyroid gland, oxyphil cells
{15059} parathyroid gland, oxyphil cells
{15060} parathyroid gland, oxyphil & chief cells
{15680} adenoma, pituitary with normal tissue
{20695} pituitary gland, both lobes
{20696} pituitary gland, both lobes
{20697} pituitary, pars distalis
{20698} pituitary, pars intermedia
{20699} pituitary, intermedia and * nervosa
{20700} pituitary, pars nervosa
{20701} adrenal gland with layers labeled, #98
{20702} adrenal gland with layers labeled, #98
{20703} adrenal gland with layers labeled, #98
{20704} adrenal gland with layers labeled, #98
{20705} adrenal gland, medulla
{20706} thyroid, normal
{20707} thyroid, normal
{20708} thyroid, normal
{20709} parathyroid, normal
{20711} pineal gland, normal
{20712} pineal gland, normal
{20795} parathyroid
{20796} parathyroid, oxyphil cell
{20797} parathyroid, oxyphil cell
{20970} hypophysis, all three regions
{20971} adenohypophysis, anterior lobe of pit.
{20972} neurohypophysis, posterior lobe pituit.
{20973} pars * Intermedia, pituitary
{20974} pars * Intermedia, pituitary
{20975} neurohypophysis, herring body
{20976} adrenal
{20977} adrenal, glomerulosa layer
{20978} adrenal, fasciculata layer
{20979} adrenal, reticularis layer
{20980} adrenal, medulla
{20981} adrenal, fasciculata
{24712} adrenal, normal
{24823} thyroid, normal
{25393} adrenal cortex, normal
{31090} pituitary in sella, normal
{34355} pituitary, normal
{36419} thyroid, normal
{36425} thyroid, normal
{36452} thyroid cytology, normal glandular cells
{36455} thyroid cytology, sheet of normal glandular cells