ENDOCRINOLOGY BOARD REVIEW Presented by Med/Peds PGY III Class

ENDOCRINOLOGY Disorders of the Hypothalamic – Pituitary Axis K. Dionne Posey, MD, MPH

ENDOCRINOLOGY Pituitary Disorders Thyroid Disorders Adrenal Disorders Gonadal Disorders Calcium Disorders Lipid Disorders

Hypothalamic–Pituitary Axis

Pituitary Gland Located within the sella tursica Contiguous to vascular and neurologic structures Cavernous sinuses Cranial nerves Optic chiasm Hypothalamic neural cells synthesize specific releasing and inhibiting hormones Secreted directly into the portal vessels of the pituitary stalk Blood supply derived from the superior and inferior hypophyseal arteries

Pituitary Gland Anterior pituitary gland Posterior pituitary gland Secrete various trophic hormones Disease in this region may result in syndromes of hormone excess or deficiency Posterior pituitary gland More of a terminus of axons of neurons in the supraoptic and paraventricular nuclei of the hypothalamus Storehouse for the hormones The main consequence of disease in this area is disordered water homeostasis

Anterior Pituitary Gland Anterior Pituitary “Master gland” Major blood source: hypothalamic-pituitary portal plexus Allows transmission of hypothalamic peptide pulses without significant systemic dilution Consequently, pituitary cells are exposed to sharp spikes of releasing factors and in turn release their hormones as discrete pulses Production of six major hormones: Prolactin (PRL) Growth hormone (GH) Adrenocorticotropin hormone (ACTH) Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Thyroid-stimulating hormone (TSH)

Anterior Pituitary Gland Anterior Pituitary “Master gland” Secreted in a pulsatile manner Elicits specific responses in peripheral target tissues Feedback control at the level of the hypothalamus and pituitary to modulate pituitary function exerted by the hormonal products of the peripheral target glands Tumors cause characteristic hormone excess syndromes Hormone deficiency may be inherited or acquired

Hypopituitarism

Gonadotropin Deficiency Women Oligomenorrhea or amenorrhea Loss of libido Vaginal dryness or dyspareunia Loss of secondary sex characteristics (estrogen deficiency) Men Loss of libido Erectile dysfunction Infertility Loss of secondary sex characteristics (testosterone deficiency) Atrophy of the testes Gynecomastia (testosterone deficiency)

ACTH Deficiency Results in hypocortisolism Pale complexion Malaise Anorexia Weight-loss Gastrointestinal disturbances Hyponatremia Pale complexion Unable to tan or maintain a tan No features of mineralocorticoid deficiency Aldosterone secretion unaffected

TSH Deficiency Hypothyroidism Atrophic thyroid gland

Prolactin Deficiency Inability to lactate postpartum Often 1st manifestation of Sheehan syndrome

Growth Hormone Deficiency Adults Often asymptomatic May complain of Fatigue Degrees exercise tolerance Abdominal obesity Loss of muscle mass Children GH Deficiency Constitutional growth delay Stimulate production of IGFs Suppressed by hyperglycemia Stimulated by hypoglycemia GH bone age < chron age CGD

Hypopituitarism Etiology Anterior pituitary diseases Common causes: Deficiency one or more or all anterior pituitary hormones Common causes: Primary pituitary disease Hypothalamic disease Interruption of the pituitary stalk Extrasellar disorders

Hypopituitarism Primary pituitary disease Hypothalamic disease Tumors Pituitary surgery Radiation treatment Hypothalamic disease Functional suppression of axis Exogenous steroid use Extreme weight loss Exercise Systemic Illness Interruption of the pituitary stalk Extrasellar disorders Craniopharyngioma Rathke pouch

Hypopituitarism

Hypopituitarism Developmental and genetic causes Acquired causes: Dysplasia Septo-Optic dysplasia Developmental hypothalamic dysfunction Kallman Syndrome Laurence-Moon-Bardet-Biedl Syndrome Frohlich Syndrome (Adipose Genital Dystrophy) Acquired causes: Infiltrative disorders Cranial irradiation Lymphocytic hypophysitis Pituitary Apoplexy Empty Sella syndrome

Hypopituitarism: Developmental and Genetic causes Septo-Optic dysplasia Kallman Syndrome Laurence-Moon-Bardet-Biedl Syndrome Frohlich Syndrome (Adipose Genital Dystrophy)

Hypopituitarism: Genetic Septo-Optic dysplasia Hypothalamic dysfunction and hypopituitarism may result from dysgenesis of the septum pellucidum or corpus callosum Affected children have mutations in the HESX1 gene involved in early development of the ventral prosencephalon These children exhibit variable combinations of: cleft palate syndactyly ear deformities hypertelorism optic atrophy micropenis anosmia Pituitary dysfunction Diabetes insipidus GH deficiency and short stature Occasionally TSH deficiency

Hypopituitarism: Developmental Kallman Syndrome Defective hypothalamic gonadotropin-releasing hormone (GnRH) synthesis Associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia May also be associated with: color blindness, optic atrophy, nerve deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic abnormalities such as mirror movements GnRH deficiency prevents progression through puberty characterized by low LH and FSH levels low concentrations of sex steroids

Hypopituitarism: Developmental Kallman Syndrome Males patients Delayed puberty and hypogonadism, including micropenis result of low testosterone levels during infancy Long-term treatment: human chorionic gonadotropin (hCG) or testosterone Female patients Primary amenorrhea and failure of secondary sexual development cyclic estrogen and progestin Diagnosis of exclusion Repetitive GnRH administration restores normal pituitary Fertility may also be restored by the administration of gonadotropins or by using a portable infusion pump to deliver subcutaneous, pulsatile GnRH

Hypopituitarism: Developmental Laurence-Moon-Bardet-Biedl Syndrome Rare autosomal recessive disorder Characterized by mental retardation; obesity; and hexadactyly, brachydactyly, or syndactyly Central diabetes insipidus may or may not be associated GnRH deficiency occurs in 75% of males and half of affected females Retinal degeneration begins in early childhood most patients are blind by age 30

Hypopituitarism: Developmental Frohlich Syndrome (Adipose Genital Dystrophy) A broad spectrum of hypothalamic lesions hyperphagia, obesity, and central hypogonadism Decreased GnRH production in these patients results in attenuated pituitary FSH and LH synthesis and release Deficiencies of leptin, or its receptor, cause these clinical features

Hypopituitarism Acquired causes: Infiltrative disorders Cranial irradiation Lymphocytic hypophysitis Pituitary Apoplexy Empty Sella syndrome

Hypopituitarism: Acquired Lymphocytic Hypophysitis Etiology Presumed to be autoimmune Clinical Presentation Women, during postpartum period Mass effect (sellar mass) Deficiency of one or more anterior pituitary hormones ACTH deficiency is the most common Diagnosis MRI - may be indistinguishable from pituitary adenoma Treatment Corticosteroids – often not effective Hormone replacement

Pituitary adenoma Lymphocytic hypophysitis

Hypopituitarism: Acquired Pituitary Apoplexy  Hemorrhagic infarction of a pituitary adenoma/tumor Considered a neurosurgical emergency Presentation: Variable onset of severe headache Nausea and vomiting Meningismus Vertigo +/ - Visual defects +/ - Altered consciousness Symptoms may occur immediately or may develop over 1-2 days

Hypopituitarism: Acquired Pituitary Apoplexy Risk factors: Diabetes Radiation treatment Warfarin use Usually resolve completely Transient or permanent hypopituitarism is possible undiagnosed acute adrenal insufficiency Diagnose with CT/MRI Differentiate from leaking aneurysm Treatment: Surgical - Transsphenoid decompression Visual defects and altered consciousness Medical therapy – if symptoms are mild Corticosteroids

Quick Quiz!!! When should you suspect pituitary apoplexy? MedStudy 2005 - Endocrine

Answer Suspect in patient presenting with Variable onset of severe headache Nausea and vomiting Meningismus Vertigo +/ - Visual defects +/ - Altered consciousness

Hypopituitarism: Acquired Empty Sella Syndrome Often an incidental MRI finding  Usually have normal pituitary function Implying that the surrounding rim of pituitary tissue is fully functional Hypopituitarism may develop insidiously Pituitary masses may undergo clinically silent infarction with development of a partial or totally empty sella by cerebrospinal fluid (CSF) filling the dural herniation. Rarely, functional pituitary adenomas may arise within the rim of pituitary tissue, and these are not always visible on MRI

Hypopituitarism Clinical Presentation Can present with features of deficiency of one or more anterior pituitary hormones Clinical presentation depends on: Age at onset Hormone effected, extent Speed of onset Duration of the deficiency

Hypopituitarism Diagnosis Biochemical diagnosis of pituitary insufficiency Demonstrating low levels of trophic hormones in the setting of low target hormone levels Provocative tests may be required to assess pituitary reserve

Hypopituitarism Treatment Hormone replacement therapy usually free of complications Treatment regimens that mimic physiologic hormone production allow for maintenance of satisfactory clinical homeostasis

Hormone Replacement Trophic Hormone Deficit Hormone Replacement ACTH Hydrocortisone (10-20 mg A.M.; 10 mg P.M.) Cortisone acetate (25 mg A.M.; 12.5 mg P.M.) Prednisone (5 mg A.M.; 2.5 mg P.M.) TSH L-Thyroxine (0.075-0.15 mg daily) FSH/LH Males Testosterone enanthate (200 mg IM every 2 wks) Testosterone skin patch (5 mg/d) Females Conjugated estrogen (0.65-1.25 mg qd for 25days) Progesterone (5-10 mg qd) on days 16-25 Estradiol skin patch (0.5 mg, every other day) For fertility: Menopausal gonadotropins, human chorionic gonadotropins GH Adults: Somatotropin (0.3-1.0 mg SC qd) Children: Somatotropin [0.02-0.05 (mg/kg per day)] Vasopressin Intranasal desmopressin (5-20 ug twice daily) Oral 300-600 ug qd

Take home points: Remember that the cause may be functional Treatment should be aimed at the underlying cause  Hypopituitarism may present Acutely with cortisol deficiency After withdrawal of prolonged glucocorticoid therapy that has caused suppression of the HPA axis. Post surgical procedure Post trauma Hemorrhage Exacerbation of cortisol deficiency in a patient with unrecognized ACTH deficiency Medical/surgical illness Thyroid hormone replacement therapy

Pituitary Tumors

Pituitary Tumors Clinical presentation: Microadenoma < 1 cm Macroadenoma > 1 cm Is the tumor causing local mass effect? Is hypopituitarism present? Is there evidence of hormone excess? Clinical presentation: Mass effect Superior extension May compromise optic pathways – leading to impaired visual acuity and visual field defects May produce hypothalamic syndrome – disturbed thirst, satiety, sleep, and temperature regulation Lateral extension May compress cranial nerves III, IV, V, and VI – leaning to diplopia Inferior extension May lead to cerebrospinal fluid rhinorrhea

Pituitary Tumors Diagnosis Treatment Check levels of all hormones produced Check levels of target organ products Treatment Surgical excision, radiation, or medical therapy Generally, first-line treatment surgical excision Drug therapy available for some functional tumors Simple observation Option if the tumor is small, does not have local mass effect, and is nonfunctional Not associated with clinical features that affect quality of life

Pituitary adenoma. Coronal T1-weighted postcontrast MR image shows a homogeneously enhancing mass (arrowheads) in the sella turcica and suprasellar region compatible with a pituitary adenoma; the small arrows outline the carotid arteries.

Adenoma Craniopharyngioma

Craniopharyngioma Derived from Rathke's pouch. Arise near the pituitary stalk extension into the suprasellar cistern common These tumors are often large, cystic, and locally invasive Many are partially calcified characteristic appearance on skull x-ray and CT images Majority of patients present before 20yr usually with signs of increased intracranial pressure, including headache, vomiting, papilledema, and hydrocephalus

Craniopharyngioma Associated symptoms include: Children Adults visual field abnormalities, personality changes and cognitive deterioration, cranial nerve damage, sleep difficulties, and weight gain. Children growth failure associated with either hypothyroidism or growth hormone deficiency is the most common presentation Adults sexual dysfunction is the most common problem erectile dysfunction amenorrhea

Craniopharyngioma Anterior pituitary dysfunction and diabetes insipidus are common Treatment Transcranial or transsphenoidal surgical resection followed by postoperative radiation of residual tumor This approach can result in long-term survival and ultimate cure most patients require lifelong pituitary hormone replacement. If the pituitary stalk is uninvolved and can be preserved at the time of surgery Incidence of subsequent anterior pituitary dysfunction is significantly diminished.

Craniophayrngioma

Quick Quiz!!! How does prolactin differ from LH/FSH in regard to hypothalamic control?

Answer Tonic hypothalamic inhibition by Dopamine

Prolactinoma Most common functional pituitary tumor Usually a microadenoma Can be a space occupying macroadenoma – often with visual field defects Although many women with hyperprolactinemia will have galactorrhea and/ or amenorrhea The absence these the two signs do not excluded the diagnosis GnRH release is decreased in direct response to elevated prolactin, leading to decreased production of LH and FSH

Prolactinoma Women Men Amenorrhea – this symptom causes women to present earlier Hirsutism Men Impotence – often ignored Tend to present later Larger tumors Signs of mass effect

Prolactinoma Essential to rule out secondary causes!! Drugs which decrease dopamine stores Phenothiazines Amitriptyline Metoclopramide Factors inhibiting dopamine outflow Estrogen Pregnancy Exogenous sources Hypothyroidism If prolactin level > 200, almost always a prolactinoma (even in a nursing mom) Prolactin levels correlate with tumor size in the macroadenomas Suspect another tumor if prolactin low with a large tumor

Prolactinoma Diagnosis Assess hypersecretion Basal, fasting morning PRL levels (normally <20 ug/L) Multiple measurements may be necessary Pulsatile hormone secretion levels vary widely in some individuals with hyperprolactinemia Both false-positive and false-negative results may be encountered May be falsely lowered with markedly elevated PRL levels (>1000 ug/L) assay artifacts; sample dilution is required to measure these high values accurately May be falsely elevated by aggregated forms of circulating PRL, which are biologically inactive (macroprolactinemia) Hypothyroidism should be excluded by measuring TSH and T4 levels

Prolactinoma Treatment Medical Surgical Cabergoline – dopamine receptor agonist Bromocriptine - dopamine agonist Safe in pregnancy Will restore menses Decreases both prolactin and tumor size (80%) Surgical Transsphenoidal surgery – irridation (if pt cannot tolerate rx)

Quick Quiz!!! What type of tumors are most prolactinomas? Prolactin levels >200 almost always indicate what? Do prolactin levels correlate with tumor size? Prolactin MedStudy 2005 - Endocrine

Answer What type of tumors are most prolactinomas? Microadenomas Prolactin levels >200 almost always indicate what? Almost always indicates prolactinoma Do prolactin levels correlate with tumor size? Yes, in macroadenomas

Growth Hormone Tumors Gigantism Acromegaly GH excess before closure of epipheseal growth plates of long bones Acromegaly GH excess after closure of epipheseal growth plates of long bones Insidious onset Usually diagnosed late

Growth Hormone Tumors May have DM or glucose intolerance Hypogonadism Large hands and feet Large head with a lowering brow and coarsening features Hypertensive – 25% Colon polyps 3-6 more likely than general population Multiple skin tags

Growth Hormone Tumors Diagnosis Treatment Screen: Confirm: Surgical Check for high IGF-I levels (>3 U/ml) Remember, levels very high during puberty Confirm: 100gm glucose load Positive: GH levels do not increase to <5ng/ml Treatment Surgical Radiation Bromocriptine - temporizing measure May decrease GH by 50% Octreotide For suboptimal response to other treatment

Quick Quiz!!! How do you screen for acromegaly? MedStudy 2005 - Endocrine

Answer Check for high IGF-I levels (>3 U/ml)

Pituitary Gland Anterior pituitary gland Posterior pituitary gland Secrete various trophic hormones Disease in this region may result in syndromes of hormone excess or deficiency Posterior pituitary gland More of a terminus of axons of neurons in the supraoptic and paraventricular nuclei of the hypothalamus Storehouse for the hormones The main consequence of disease in this area is disordered water homeostasis

Posterior Pituitary Gland The Neurohypophysis Major blood source: the inferior hypophyseal arteries Directly innervated by hypothalamic neurons (supraopticohypophyseal and tuberohypophyseal nerve tracts) via the pituitary stalk Sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus

Posterior Pituitary Gland Production of Vasopressin (antidiuretic hormone; ADH; AVP) Oxytocin Acts on the renal tubules to reduce water loss by concentrating the urine Deficiency causes diabetes insipidus (DI), characterized by the production of large amounts of dilute urine Excessive or inappropriate production predisposes to hyponatremia if water intake is not reduced in parallel with urine output Stimulates postpartum milk letdown in response to suckling

Posterior Pituitary Gland Vasopressin (Anti Diuretic Hormone) Some control via anterior hypothalamus Contains separate osmoreceptors which aid in ADH release and thirst regulation Osmotic stimulus Sodium Mannitol Non osmotic factors Blood pressure and volume at extremes Nausea Angiotensin II Insulin induced hypoglycemia Acute hypoxia Acute hypercapnia

Posterior Pituitary Gland Rapidly secreted in direct proportion to serum osmolality Increased with Aging Hypercalcemia Hypoglycemia Lithium treatment Volume contraction Decreased with Hypokalemia Threshold set point Increased Hypervolemia, Acute hypertension, Corticosteroids Decreased Pregnancy, Pre-menses, Volume contraction

Diabetes Insipdus Etiology Deficient AVP can be primary or secondary The primary form Deficiency in secretion Agenesis or irreversible destruction of the neurohypophysis Malformation or destruction of the neurohypophysis by a variety of diseases or toxins Neurohypophyseal DI, Pituitary DI, or Central DI Deficiency in action Can be genetic, acquired, or caused by exposure to various drugs Nephrogenic DI It can be caused by a variety of congenital, acquired, or genetic disorders 50% idiopathic

Diabetes Insipdus Gestational DI Primary deficiency of plasma AVP Result from increased metabolism by an N-terminal aminopeptidase produced by the placenta Signs and symptoms manifest during pregnancy and usually remit several weeks after delivery

Diabetes Insipdus Secondary deficiencies of AVP Results from inhibition of secretion by excessive intake of fluids Primary polydipsia Dipsogenic DI characterized by an inappropriate increase in thirst caused by a reduction in the "set" of the osmoregulatory mechanism. association with multifocal diseases of the brain such as neurosarcoid, tuberculous meningitis, or multiple sclerosis but is often idiopathic. Psychogenic polydipsia is not associated with thirst polydipsia seems to be a feature of psychosis Iatrogenic polydipsia results from recommendations of health professionals or the popular media to increase fluid intake for its presumed preventive or therapeutic benefits for other disorders

Diabetes Insipdus Secondary deficiencies of AVP Antidiuretic response to AVP Results from polyuria Caused by washout of the medullary concentration gradient and/or suppression of aquaporin function. Usually resolves 24 to 48 h after the polyuria is corrected Often complicate interpretation of tests commonly used for differential diagnosis

Diabetes Insipdus Pathophysiology When secretion or action of AVP is reduced to <80 to 85% of normal urine concentration ceases and the rate of output increases to symptomatic levels Primary defect (pituitary, gestational, or nephrogenic DI) Polyuria results in a small (1 to 2%) decrease in body water and a commensurate increase in plasma osmolarity and sodium concentration that stimulate thirst and a compensatory increase in water intake Overt signs of dehydration do not develop unless the patient also has a defect in thirst or fails to drink for some other reason

Diabetes Insipdus Pathophysiology Primary polydipsia Pathogenesis of the polydipsia and polyuria is the reverse of that in pituitary, nephrogenic, and gestational DI Excessive intake of fluids slightly increases body water, thereby reducing plasma osmolarity, AVP secretion, and urinary concentration. Results in a compensatory increase in urinary free-water excretion that varies in direct proportion to intake Clinically appreciable overhydration uncommon unless the compensatory water diuresis is impaired by a drug or disease that stimulates or mimics endogenous AVP

Diabetes Insipdus Clinical Presentation Production of abnormally large volumes of dilute urine The 24-h urine volume is >50 mL/kg body weight and the osmolarity is <300 mosmol/L. The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. It is also associated with thirst and a commensurate increase in fluid intake (polydipsia). Clinical signs of dehydration are uncommon unless fluid intake is impaired.

Diabetes Insipdus Diagnosis Verify polyuria Check osmolarity a 24-h urine output collection > 50 mL/kg per day (>3500 mL in a 70-kg man). Check osmolarity >300 mosmol/L due to a solute diuresis and the patient should be evaluated for uncontrolled diabetes mellitus or other less common causes of excessive solute excretion <300 mosmol/L Due to water diuresis and should be evaluated further to determine which type of DI is present

Diabetes Insipdus Diagnosis Water deprivation test If does not result in urine concentration before body weight decreases by 5% or plasma osmolarity/sodium exceed the upper limit of normal (osmolarity >300 mosmol/L, specific gravity >1.010) Primary polydipsia or a partial defect in AVP secretion or action are largely excluded Severe pituitary or nephrogenic DI are the only remaining possibilities

Diabetes Insipdus Diagnosis: Neurogenic vs Nephrogenic Administer Desmopressin (DDAVP) 1 g 0.03 ug/kg subcutaneously or intravenously Measure urine osmolality (30,60,120 min) 1 to 2 h later An increase of >50% indicates severe pituitary DI Smaller or absent response is strongly suggestive of nephrogenic DI

Diabetes Insipdus Treatment Neurogenic DI Nephrogenic DI DDAVP Chlorpropamide (Diabinese) Antidiuretic effect can be enhanced by cotreatment with a thiazide diuretic SE: hypoglycemia, disulfiram like reaction to ethanol Contraindicated in Gestional DI Nephrogenic DI Not affected by treatment with DDAVP or chlorpropamide May be reduced by treatment with a thiazide diuretic and/or amiloride in conjunction with a low-sodium diet Inhibitors of prostaglandin synthesis (e.g., indomethacin) are also effective in some patients Psychogenic or dipsogenic DI there is no effective treatment

Syndrome of Inappropriate ADH secretion Etiology CNS Lesions, Inflammatory disease Trauma, psychosis Drugs Stimulate AVP release Nicotine, phenothiazines, TCAs, SSRIs Chlorpropamide, clofibrate, carbamazepine, cyclophosphamide, vincristine Pulmonary Infection Mechanical/ventilatory issue

Syndrome of Inappropriate ADH secretion Pathophysiology Excessive AVP production resulting in decreased volume of highly concentrated urine Water retention Decreased plasma osmolarity Decreased plasma Na

Syndrome of Inappropriate ADH secretion Clinical Presentation Acute Water intoxication Headache, confusion Nausea, vomiting Anorexia Coma, convulsions Chronic May be asymptomatic

Syndrome of Inappropriate ADH secretion Diagnosis Diagnosis of exclusion AVP level inappropriately elevated relative to plasma osmolality

Syndrome of Inappropriate ADH secretion Treatment Acute Fluid restriction Hypertonic saline Central myelinolysis Chronic Demeclocyline 150-300mg PO TID-QID Reversible Nephrogenic DI Insensible losses ~500ml/day; so intake should be ~500 less than UO Quadraparesis, ataxia, abn extraocc movements 3% saline </= 0.05ml/kg/min; stat check NA q 2hr Stop once inreases by 12mmol or to 130mmol/L Watch UO

Treatment Guidelines See Handout

References Harrison's Principles of Internal Medicine - 16th Ed. (2005) Up to Date Med Study – Endocrine Mayo Clinic Board Review

Questions

True or False The pituitary: Pituitary tumors are usually macroadenomas. Lack of galactorrhea essentially rules out a prolactinoma. Prolactin levels correlate with the size of a prolactinoma Prolactin level of 230 in a nursing woman is probably due to a prolactinoma An enlarged sella tursica can be seen in a hypothyroid patient.

Answers The pituitary: Pituitary tumors are usually macroadenomas. – True Lack of galactorrhea essentially rules out a prolactinoma. – False Prolactin levels correlate with the size of a prolactinoma – True Prolactin level of 230 in a nursing woman is probably due to a prolactinoma – True An enlarged sella tursica can be seen in a hypothyroid patient. – True MedStudy 2005 - Endocrine

A 24 year old woman complains of fatigue and malaise A 24 year old woman complains of fatigue and malaise. She gave birth to a healthy infant 4 months before presentation. She did not breastfeed. Menses have subsequently been irregular and infrequent, representing a change from before pregnancy. The family history is notable for a sister who has Hashimoto thyroiditis. The pregnancy test is negative, and the serum level of prolactin is normal. Of interest, TSH is 0.9mIU/L (normal, 0.3-5.0) and free thyroxine is 0.8ng/dL (normal, 0.8-1.4). The results of MRI of the pituitary are reported as normal. The next step would be to: Lymphocytic Hypophysitis

A) Start thyroxine replacement therapy B) Request a neurosurgeon to perform a biopsy of the pituitary Perform a water deprivation test Perform a 1 µg corticotropin (ACTH) stimulation test Measure IGF-1

A) Start thyroxine replacement therapy B) Request a neurosurgeon to perform a biopsy of the pituitary C) Perform a water deprivation test D) Perform a 1 µg corticotropin (ACTH) stimulation test E) Measure IGF-1

A 38-year-old woman is referred to you by her gynecologist A 38-year-old woman is referred to you by her gynecologist. She first presented to her gynecologist 4.5 years ago with amenorrhea of 3 years’ duration and galactorrhea of 1 year’s duration. She had been taking no medications, and her initial physical examination was unremarkable except for expressible galactorrhea bilaterally. A routine chemistry screen was normal; her T4 level was 7.8 µg/dL, serum TSH was 1.4 µU/mL, and prolactin level was 48.2 ng/mL. After taking bromocriptine for 2 months, her prolactin level was 19 ng/mL, at which point her galactorrhea ceased and she had her first menstrual period in 3 years. She continued to take bromocriptine over the next 4 years; her prolactin level remained less than 20 ng/mL, and she continued to have regular periods. However, she stopped taking her bromocriptine 6 months ago and is now having progressively worse headaches.

Her prolactin level is now 60 Her prolactin level is now 60.5 ng/mL, and a visual field examination shows a small superotemporal field cut in the right eye. A computed tomographic (CT) scan shows a 2.4-cm ´ 1.6-cm sellar mass with considerable suprasellar extension. She is now referred to you for further management.   What is the most likely diagnosis? (A) Prolactinoma (B) Clinically nonfunctioning pituitary adenoma (C) Metastatic cancer to the sella (D) Craniopharyngioma

What is the most likely diagnosis?   (A) Prolactinoma (B) Clinically nonfunctioning pituitary adenoma (C) Metastatic cancer to the sella (D) Craniopharyngioma