(From Path book and lecture, 30 Jan 2001, by Brian Buschman)
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The anterior pituitary is made of eosinophils, basophils and chromophobic cells that release various hormones when stimulated.
The acidophils include lactotrophs that release prolactin and somatotrophs that release GH. Basophile include thyrotrophs that make TSH, gonadotrophs making FSH and LH and corticotrophs that cleave proopiomdanocortin (POMC) into ACTH and MSH.
Pituitary dysfunction can be categorized into effects of hyperpituitarism, hypopituitarism and mass effects such as enlargement.
Rare causes of hyperpituitarism may be from a general primary hypothalamic disease (too much releasing hormone), a primary hyperplasia where the pituitary just makes too much or from a functioning carcinoma. But all three of these cases are very rare.
More than likely hyperpituitarism is caused by a proliferation (adenoma) of one or more of the cell types. The most common being mixed cell adenomas that release both GH and Prl.
Hyperprolactinemia is the most common cause of pituitary hyper-function. IT clinically shows amenorrhea, galactorrhea, loss of libido and infertility. Sometimes it even shows gynecomastia.
Hyperprolactemia may also be caused by trauma or the so-called stalk effect where pressure on the hypothalamus causes decrease in the release of stimulating factors.
Anti-dopamine drugs, estrogen therapy and primary hypothyroidism ( TRH) all can cause hyperprolactinemia.
Treatment is first by bromocriptine, a dopamine agonist, that suppresses growth and Prl production. If that is not effective it can be treated by radiation or transsphenoidal surgery.
GH secreting neoplasms are the second most common type. The excess GH has two different effects in the pre and post-pubescent individuals. In children it leads to gigantism and generally large body size. In adults it causes acromegally with enlargement of the skull, mandible, facial bones, hands, feet, organs and so on. It can lead to diabetes, hypertension, muscle weakness, arthritis, gonadal dysfunction and CV disease. A buzzword for acromegally is “sausage-like” fingers.
As states many somatotroph adenomas secrete both GH and Prl and more express the gsp oncogene. This oncogene messes up the binding sites for GH and Prl so the system things there is less than there really is.
GH acts to increase hepatic secretion of IGF-1 (insulin-like growth factor) so diagnosis of somatotrophic adenoma can be made with the increased levels of GH and IGF-1. You may or may not see elevated Prl. Confirmation is via glucose suppression test or imaging scans like MRI (it’s better that using CT).
Treatment can be via transsphenoidal surgery, radiation or octreotide acetate. Radiation is a last resort because it may lead to a future pituitary hyperplasia. Octreotide acetate is an analogue of somatostatin that function to help suppress GH release.
Corticotrophic adenomas are ACTH secreting tumors. They can be recognized histologically by PAS staining for carbohydrate in POMC.
Increased ACTH leading to increased adrenal hemorrhages (like cortisol, epi and androgens) is called Cushing’s disease. If increased adrenal hormone secretion is caused by another cause (like adrenal tumor) it’s called Cushing’s syndrome.
Signs include central deposition of fat from excess cortisol as well as peripheral muscle wasting. Such people have moon faces, buffalo humps, truncal obesity, abdominal striae and often diabetes, hirsutism (extra body hair) and amenorrhea from androgen secretion.
Diagnosis is via 24-hr urine collection for cortisol and 17-hydroxycorticosteroids. Plasma ACTH, MRI and dexamethasone suppression test are also used. The dexamethasone suppression test will suppress Cushing’s syndrome since the pituitary, where the negative feedback takes place, is still working properly. It will not suppress Cushing’s disease since the pituitary is broken. If it’s an extrapituitary tumor the dexamethasone test does nothing.
Occasionally you will see a gonadotrophs adenoma in women or middle aged men. They show decreased libido (men), amenorrhea or galactorrhea. Most common symptoms are related to mass effects.
Once in a while there is a thyrotrophs adenoma making excess TSH. Which will cause classic hyperthyroidism.
Hypopituitarism is caused by:
1) Nonsecretory pituitary adenoma
2) Ischemic necrosis
3) Ablation of the pituitary by surgery or radiation
Hypothalamic lesions may include 2o metastatic carcinoma (breast and lung), infections, gliomas, tetratomas and craniopharyngioma. Pituitary lesions are often nonsecretory adenomas. Surgical/radiation damage that messes up 75% of the gland or Sheehan’s syndrome.
Effects include isolated hormone deficiencies such as GH or LF in adults. Panhypopituitarism can also occur causing hypothyroidisms and hypoadrenalism in adults. In kids it causes dwarfism and infantilism (retarded physical and sexual growth).
Hypothalamic neoplasms, also called suprasellar, include:
1) Craniopharyngioma (MC)
2) Gliomas
3) Germ cell tumors
Most of the effects are from the mass effects of the given tumor.
Craniopharyngiomas are 3-5% of all cranial tumors and appear in the 20’s and 30’s. They are from remains of Rathke’s pouch and can arise in the hypothalamus and press on the optic chiasm. That can cause a bitemporal hemianopia. They are benign tumors of squamous and columnar epithelia. Calcification is another feature.
Non-secreting adenomas are diagnosed later than most similar tumors because they do not produce symptoms until they are large enough to exhibit mass effects. They cause headache and hypohormonal problems. Since they are nonsecretory all stains for hormones will be negative.
Young women may experience Sheehan’s syndrome which is a postpartum ischemic damage to at least 75% of the pituitary. It is caused because during pregnancy the anterior pituitary doubles in size and the low pressure portal system is unable to supply it all. After birth there is an abrupt onset of hyperperfusion causing reperfusion injury.
Symptoms include failure of lactation (no Prl), hypothyroidism (no TSH), hypoadrenalism (no ACTA), decreased skin pigmentation (no MSH) and amenorrhea (no LH and FSH). Luckily the posterior lobe is usually not affected.
The posterior pituitary makes oxytocin (shortage shows no symptoms) and ADH. ADH causes the reabsorption of FREE WATER (hypervolemia and hyponatremia). Problems include:
1) Diabetes insipidus (ADH deficiency) causing decreased reabsorption of water, the inability to concentrate urine, polyuria, polydypsia, hypovolemia and hypernatremia. It may be by a 1o lesion or may be idiopathic.
2) SIADH (syndrome of inappropriate ADH). This leads to excess water reabsorption, inability to dilute urine, hypervolemia, hyponatremia and cerebral edema.
The MCC of SIADH is from a small cell carcinoma (Oat-cell carcinoma).
Treat these two by appropriate restriction or addition of fluid and/or salt intake.
The thyroid gland develops of the pharyngeal apparatus and initially has a thyroglossal duct. It’s fairly common for parts to persist and cause cysts in adults. Don’t worry as they are just cysts and not cancer
The thyroid has two functions:
1) Parafollicular cells (c-cells) make calcitonin which causes osteoclasts to stop breaking down bone therefore lowering serum Ca++. They show up well with a calcitonin stain.
2) Follicular cells and the colloid material make and hold T4 (thyroxin) and T3 (triiodothyrosine) until it’s time for release. When stimulated by TSH they release T3 and T4 to circulate while bound to thyroxin BG.
T3 and T4 upregulate lipid and carbohydrate and protein synthesis. They increase the BMR.
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