ENDOCRINOLOGY

ENDOCRINOLOGY- pituitary

Surrounded by sphenoid bone,cover by sellar diaphragm.2 lobes: Adenohypophysis ( anterior) Neurohypophysis (posterior)Hypothalamus-pituitary axisPituitary gland- general

Pituitary gland

Summary of action

Microadenoma1cmLarge tumor can compress the optic chiasm and can cause visual deficits(Bitemporal hemianopsia).Microadenoma are more common than macroadenoma

Disease of Anterior Pituitary

Prolactin - 50-60%Growth hormone - 15-20%ACTH - 10-15%Gonadotroph - 10-15%Pituitary adenoma by function

A 30 year old women comes to your office because of milk-like discharge for over 4 weeks. She also states that she has not menstruated in 2 months. Her examination reveals galactorrhea but is otherwise normal.What is the next most appropriate test?What is the nxt most appropriate management?

Hyperprolactinemia

Physiology cause: Pregnancy, intense exercise , renal insufficiency, and increase chest wall stimulationTumors: Functional pituitary adenomaDrugs : antipsychotic drug, methyldopa, metochlopromide, opioids, TCA, verapamil.Primary hypothyroidism (increase TRH and increase prolactin release)>>check TSHHyperprolactinemia - Etiology

Women Galactorrhea, amenorrhea and infertility.MenErectile dysfunction and decrease libido, gynecomastia(rare).

Hyperprolactinemia-Presentation

After prolactin level is found to be high ,perform:Thyroid function test (check TSH)Pregnancy testBun/creatinine (kidney disease elevates prolactin) Liver function tests ( cirrhosis elevates prolactin)Exclude drugsMRI is done after :High prolactin level>100ng/mlSecondary cause like medication are excludedPt is not pregnantHyperprolactinemia- diagnostic test

Dopamine agonist: Carbegoline is better tolerated than bromocriptine2. Transphenoidal surgery is appropriate for those not responding to medication.3. Radiation is rarely needed.Hyperprolactinemia - treatment

ACROMEGALY

A 52 year-old man complains of increased hat size and headaches when he wakes up in the morning. He is a famous wrestler. Physical exam reveals mild diastolic HTN, prominant jaw with spaces between the teeth, large hands and feet, and generalized muscle weakness.Acromegaly

-overproduction of growth hormone leading to soft tissue overgrowth throughout the bodyACROMEGALY - Definition :

MCC pituitary adenoma. Association with one of the multiple endocrine neoplasias when it is combined with parathyroid and pancreatic disorders like gastrinoma or insulinoma.Rarely, acromegaly is caused by ectopic GH or GHRH production from a lymphoma or bronchial carcinoid.Acromegaly - etiology

Acromegaly enlarges soft tissue like cartilage and bone, resulting in: Increased hat, ring, and shoe size Carpal tunnel syndrome(bilateral) and obstructive sleep apnea from soft tissues enlarging Body odor from sweat gland hypertrophy Coarsening facial features and teeth widening from jaw growth Deep voice and macroglossia (big tongue)Acromegaly - Clinical finding:

Colonic polyps and skin tags Arthralgias from joints growing out of alignment Hypertension for unclear reasons in 50% Cardiomegaly and CHF(MCC of death)Erectile dysfunction from increased prolactin co-secreted with the pituitary adenomaDiabetes/impair glucose toleranceAcromegaly - Clinical finding:

Insulin growth factor-1 (IGF-1)Confirmatory testing involves measurement of GF after 100g of glucose is given orally,this test is positive if GH remains high(>5ng/ml) and suggests acromegaly. Normally,a glucose load should completely supress level of GH.2. MRI should be done only after the laboratory identification of acromegaly.Acromegaly - Diagnostic

1. Surgery: Acromegaly responds to transphenoidal resection of the pituitary in 70% of cases. Larger adenomas are harder to cure.2. Medications: Cabergoline: Dopamine will inhibit GH release. Octreotide or lanreotide: Somatostatin inhibits GH release. Pegvisomant: A GH receptor antagonist, it inhibits IGF release fromthe liver.3. Radiotherapy: Radiation is used only in those who do not respond to surgeryor medications.Acromegaly-treatment

Pressure of tumor surrounding structures ,invasion of tumor into brain, sinusesCardiac failure (most common cause of death)Diabetes mellitusCord compressionVisual field defectAcromegaly - Complication

A 42-year-old man presents to a new family physician to establish care. According to the patient, he has been healthy his entire life and rarely visits doctors, although he recently got married and his wife insisted that he see a doctor at least once. He reports no past medical or surgical history. His physical exam is notable for an elevated blood pressure (150/90), and the findings seen in Figures A and B. What will be the most likely cause of death for this patient?

1. Respiratory disease2. Cardiovascular disease3. Malignancy4. Chronic kidney disease5. Liver failure

Correct answer =2this patient has acromegaly, the most common cause of death from which is cardiovascular disease.

Acromegaly is defined by an excess of growth hormone. This most commonly occurs in the setting of a pituitary adenoma, but may also occur due to other factors (see illustration A). The excess growth hormone in acromegaly results in significant organomegaly. In the case of the cardiovascular system, patients can develop hypertension, left ventricular hypertrophy, asymmetric septal hypertrophy, diastolic heart failure, and even cardiomyopathy. Treatment of acromegaly involves resection of the pituitary adenoma when possible and medical management of growth hormone excess with somatostatin analogues.

Lake et al. review pituitary adenomas. They note that the most common types of pituitary adenomas are prolactinomas and non-functioning adenomas. Acromegaly, hyperprolactinemia and Cushing's syndrome can result from pituitary adenomas.

Ciresi et al. examine the metabolic characteristics of newly acromegalic patients. In an examination of 307 newly diagnosed patients, they noted that women have a higher rate of metabolic syndrome, insulin resistance and visceral adiposity dysfunction in this disease.

Figure A shows the typical facial changes that accompany acromegaly: prominent cheekbones, bulging forehead, and an enlarged jaw.

Figure B shows a close up of the prominent brow ridge that may be seen in patients with acromegaly.

Panhypopituitarism is caused by any condition that compresses or damages the pituitary gland. Tumors of many types can compress the gland, such as metastatic cancer, adenomas, Rathke cleft cysts, meningiomas, craniopharyngiomas,or lymphoma. Trauma and radiation are damaging to the pituitary.Inflammatory disease: granulomatous ds(sarcoidosis, tb,syphilis), autoimmune and lymphocytic infiltrationVascular ds: sheehan postpartum necrosis and infiltrative ds include hemochromatosis and amyloidosisStroke.Hypopituitarism-etiology

SHEEHAN SYNDROME Postpartum hemmorhage-induced infarction of the pituitary gland result of hypovolemic shock pituitary normally very enlarged during pregancy due increased lactotrophs there is no corresponding increase in blood supply to the pituitary gland and can infarct when systemic blood pressure drop hypopituitarism results in reduced prolactin secretionSymptoms sudden cessation of lactation or failure to commence lactation loss of prolactin fatigue loss of TSH loss of pubic and axillary hair loss of LH/FSH anorexiaEvaluation Only clinically significant cause of lower than normal serum prolactin levels Imaging MRI shows infarction of the pituitary gland

5 days post-vaginal delivery, a 26-year-old woman presents to her pediatrician with the inability to breast feed her child. History reveals that her vaginal delivery was complicated by a postpartum hemomorhage.Sheehan syndrome

A 28-year-old G2P1 female with a history of hypertension presents to the emergency room at 33 weeks with headache and blurry vision. On exam, her vitals include BP 186/102 mmHg, HR 102 beats per minute, RR 15 breaths per minute, and T 98.9 degrees Fahrenheit. She undergoes an immediate Caesarian section, and although she is noted to have large-volume blood loss during the procedure, the remainder of her hospital course is without complications. Four weeks later, the patient returns to her physician and notes that she has had blurry vision and has not been able to lactate. A prolactin level is found to be 10 ng/mL (normal: 100 ng/mL). Which of the following is the most appropriate next step? Topic Review Topic

1. Galactogram2. Observation of materal-child interactions3. Brain MRI4. Head CT5. Breast ultrasound

PREFERRED RESPONSE 3This patient's clinical condition is consistent with Sheehan's syndrome, which is best diagnosed with a brain MRI.

Sheehan's syndrome is characterized by peripartum pituitary necrosis due to hypotension during or immediately after childbirth. During pregnancy, increased lactotrophs cause enlargement of the pituitary gland without a corresponding increase in blood supply. This makes the pituitary gland particularly vulnerable to infarction due to hypotension. The major characteristics of Sheehan's syndrome are explained by the loss of pituitary hormone products, including thyroid stimulating hormone (symptoms of hypothyroidism), prolactin (inability to lactate), and gonadotrophs (loss of pubic hair). Treatment of the condition includes life-long hormone replacement.

Samra discusses the ocular complications of Sheehan's syndrome. She notes that pituitary hemorrhage and swelling from infarction can impact the neighboring ocular structures. Overall, 78% of patients with Sheehan's syndrome have opthalmoplegia and 64% have decreased visual acuity.

Soares et al. performed a case-control study to evaluate the effects of long-term growth hormone replacement in patients with Sheehan's syndrome. They find that hormone treatment is associated with a decreased high-density lipoprotein and visceral fat and increased rates of glucose intolerance.

Incorrect Answers:Answer 1: Galactogram should be considered if the cause of this patient's inability to lactate is thought to be structural.Answer 2: There is no indication that this patient has poor maternal-child interactions.Answer 4: Although pituitary infarct is visible on head CT, the more sensitive imaging test is a head MRI.Answer 5: Breast ultrasound is useful for diagnosing a breast abscess, which can cause a plugged duct. Abscesses are usually unilateral, and may be associated with breast tenderness and fever.

Illustration A shows a T1-weighted head MRI with gadolinium showing an enlarged, rim-enhancing pituitary gland, suggesting Sheehan's syndrome with non-hemorrhagic pituitary ischemia.

Prolactin deficiency: There are never any symptoms of prolactin deficiency in men. In women, prolactin deficiency inhibits lactation after childbirth.(LH) and follicle-stimulating hormone (FSH): Women will not be able to ovulate or menstruate normally and will become amenorrheic.Men will not make testosterone or sperm. Both will have decreased libido and decreased axillary, pubic, and body hair. Men will have erectile dysfunction and decreased muscle massHypopituitarism clinical findings

Growth hormone (GH) deficiency: Children present with short stature and dwarfism.Adults have few symptoms of GH deficiency because several other hormones, such as catecholamines, glucagon, and cortisol, act as stress hormones.Adults deficient in GH have subtle findings such as: Central obesity Increased LDL and cholesterol levels Reduced lean muscle massHypopituitarism clinical findings

Hyponatremia is common secondary to hypothyroidism and isolated glucocorticoid underproduction. Potassium levels remain normal because aldosterone is not affected and aldosterone excretes potassium.MRI detects compressing mass lesions on the pituitary.Diagnostic Tests

Older, Less Useful Tests Metyrapone: Metyrapone inhibits 11-beta hydroxylase. This decreases the output of the adrenal gland. Metyrapone should normally cause ACTH levels to rise because cortisol goes down. Cortisol is the feedback inhibition on the pituitary. Insulin stimulation: When insulin decreases glucose levels, GH should usually rise. Failure of GH to rise in response to insulin indicates pituitary insufficiency.Diagnostic Tests

Low (TSH) and low thyroxine levelsDecreased TSH response to (TRH)Decreased ACTH and decreased cortisol levelNormal response to cosyntropin stimulation of the adrenal.Cortisol will rise (adrenal is normal) in recent disease, but a bnormal in chronic disease because of adrenal atrophy.No response (rise) in ACTH level with CRH.An elevated baseline cortisol level excludes pituitary insufficiency.Specific diagnostic test for each hormone

Replace deficient hormones with: Cortisone Thyroxine Testosterone and estrogen Recombinant human growth hormoneReplace cortisone before starting thyroxine.Treatment

Empty sella syndrome (ESS)

Caused by herniation of the suprasellar subarachnoid space through an incomplete diaphragm sella.No pituitary gland is visible on CT/MRI.Most patient are obese, multiparous womens with headache,30% will have hypertension; endocrine symptoms are less.ESS

Posterior pituitary gland

Definition: Diabetes insipidus (DI) is a decrease in either the amount of ADH from the pituitary (central DI) or its effect on the kidney (nephrogenic DI).Diabetes insipidus (DI)

25 year old male complains of a unabated thirst that began three weeks ago. He is constantly drinking and goes to the bathroom around five times a night. He has lost five pounds over the last few weeks, and is on lithium for a bipolar disorder. His BP is 115/70.Diabetes insipidus (DI)

Central DI (CDI): Any destruction of the brain from stroke, tumor, trauma,hypoxia, or infiltration of the gland from sarcoidosis or infection can cause CD I.Nephrogenic DI (NDI): kidney diseases such as chronic pyelonephritis, amyloidosis, myeloma, sickle cell disease Hypercalcemia(severe dehydrate)HypokalemiaDrugs:lithium,demeclocycline,colchicineDI-Etiology

Polyuria,polydipsiaExcessive dilute urineHypernatremia(losing free water) if severe develop neurological symptoms such as confusion, disorientation, lethargy,and eventually seizures and coma. Neurological symptoms occur only when volume losses are not matched with drinking enough fluidLow urine osmolalityIncrease serum osmolalityClinical finding

Water restriction test

Central DI is treated with long-term vasopressin (desmopressin) use.Nephrogenic DI is managed by trying to correct the underlying cause (e.g.,hypokalemia or hypercalcemia). Also responds to hydrochlorothiazide,amiloride, and prostaglandin inhibitors such as NSAIDs (e.g.,indomethacin).Treatment

A 45-year-old female undergoes a transphenoidal approach for a pituitary prolactinoma. Surgery proceeded without complications and the entire mass was removed. The patients urine output is 4 L on post-operative day 1, and labs are significant for serum Na of 145 mEq/L (normal: 135-145). Urine osmolality is 185 mOsm/kg, and urine specific gravity is 1.004 (normal: 1.012 to 1.030). Which of the following choices is the next best step? 1. Water restriction2. Loop diuretic3. CT scan of the brain4. 0.45% NaCl administered intravenously5. Desmopressin

PREFERRED RESPONSE 5

The patients history and lab results are consistent with post-surgical central diabetes insipidus. The most reasonable next step is administration of desmopressin or chlorpropamide.

Diabetes insipidus (DI) can be classified as central or nephrogenic. Central DI is caused by a deficiency in antidiuretic hormone (ADH) secretion, while nephrogenic DI is caused by resistance to ADH. In this situation, the patient has recently undergone transphenoidal resection of a pituitary adenoma and central DI is a known complication. Symptoms of central DI include polyuria, nocturia, and polydipsia. Lab work typically shows elevated serum sodium, low urine osmolality (50-200 mOsm/kg), and elevated serum osmolality. First line treatment for central DI is administration of desmopression, an ADH analog. Alternatively, chlorpropamide, carbamazepine, and thiazide diuretics have also been used to treat central DI.

Kugler and Hustead discuss the approach to serum sodium imbalance in the elderly. They discuss common causes of hyponatremia, such as medications, glucocorticoid deficiency, hypothyroidism, polydipsia, and SIADH, which is the opposite of DI. They also discuss common causes of hypernatremia, including primary hypodipsia and DI, and present an algorithm for the workup of hypernatremia.

Schreckinger et al. discuss the development of DI following pituitary tumor resection, commenting that the course of DI has three patterns - transient, permanent, and triphasic. Transient DI tends to resolve after 3-5 days, permanent DI occurs when the hypothalamus or infundibulum are damaged, while triphasic is a combination of the two and results from hypothalamic neuronal shock.

Incorrect answers:Answer 1: Water restriction can be used to distinguish central DI from primary polydipsia - however, in this situation, the clinical picture points toward central DI.Answer 2: Loop diuretics are not used in the treatment of DI.Answer 3: CT scan of the brain would likely reveal post-operative changes, but not help diagnose DI.Answer 4: Administration of fluids would not be sufficient for treatment of D

SIADHMrs. Jones, a type II diabetic, presents with mental status changes. She is taking 250 mg of chlorpropamidedaily. Physical exam is unremarkable. Lab studies show Na 120, K of 3.2, Cl of 90, bicarb of 21, glucose of 14, and BUN of 5. Random urine sodium is 80 with a urine osmolarity of 306.

Free water retentionECF volume expansionEuvolumic hyponatremiaNo EDEMA or hypertension(escape mechanism)NatriuresisSymptoms when hyponatremia is severe:1.Irritability2.Confusion3. SeizureSIADH

Pulmonary disorders:Malignancy(oat cells,small cell carcinoma)TB,sarcoidosisLung abscessCNS DisorderHead injuryCerebral vascular accident(stroke)EncephalitisDrugsChlorpropamideVincristine,vinblastine,cyclophosphamideSSRI(sertraline)CarbamazepineclofibrateSIADH-Etiology

Hyponatremia