Morning Report

1. Morning Report Week of July 1-5

2. Objectives Discuss the hormonal makeup of the anterior and posterior pituitary Be able to list a differential for hyperprolactinemia Understand the different types of pituitary adenomas, focusing specifically on prolactinomas and GH secreting adenomas Be able to diagnose and treat prolactin adenomas and GH secreting adenomas

3. Pituitary Gland Lies in the sella turcica within the sphenoid bone Lateral border: cavernous sinus (contains carotid arteries, CN III, IV, VI) Superior border: optic chiasm Inferior border: roof of the sphenoid sinus

4. Pituitary Gland Anterior Pituitary (adenohypophysis) Somatotropin (GH) Prolactin Corticotropin (ACTH) Thyrotropin (TSH) LH FSH Posterior Pituitary (neurohypophysis) Vasopressin (AVP) Oxytocin

5. Pituitary Gland Anterior Pituitary Regulated by positive and negative feedback Stimulated by hypothalamic hormone and inhibited by a target organ hormone via the hypothalamic-pituitary portal circulation Except prolactin, which is under inhibitory control by hypothalamic dopamine neurons Posterior Pituitary An extension of the central nervous system

6. Differential of Hyperprolactinemia Physiologic Pregnancy Usually ~200s by time of delivery (range 35-600) Due to increased levels of estradiol Nipple stimulation Due to a neural mechanism Proportional to degree of lactotroph hyperplasia Not usually seen in non-lactating women Stress Physical or psychological More common on women because of increased estradiol concentrations on lactotroph cells

7. DDx of Hyperprolactinemia Pathologic Prolactinoma (levels up to 50,000) Decreased dopaminergic inhibition of prolactin Drug use Typical and atypical antipsychotics Reglan Cimetidine Methyldopa Verapamil Codeine, Morphine

8. DDx of Hyperprolactinemia Chest wall lesions Due to a neural mechanism (similar to nipple stimulation) Burns, spinal cord lesions, post thoracotomy CRF Decreases clearance Primary hypothyroid TRH stimulates prolactin production Hypothalamic and Pituitary processes i.e. Infiltrative disease, craniopharyngioma Cause “stalk effect” Ectopic production Ovarian tumors Hypothalamic and pituitary disease: tumors of hypothalamus (craniopharyngiona, metastatic breast Ca), infiltrative dz of hypothal (sarcoid), section of hypothalamic-pituitary stalk (head trauma, surgery), other adenomas of the pituitary) Hypothalamic and pituitary disease: tumors of hypothalamus (craniopharyngiona, metastatic breast Ca), infiltrative dz of hypothal (sarcoid), section of hypothalamic-pituitary stalk (head trauma, surgery), other adenomas of the pituitary)

9. Pituitary Adenomas Benign adenomas originating from monoclonal expansion of a certain cell type of the pituitary Mechanisms by which the tumors cause symptoms: Mass effect (HA, visual changes, CN dysfunction) Endocrine hyperfunction Treatment: Medication and/or Transsphenoidal surgery (TSS) Bitemporal hemianopia b/c of extension on the suprasellar space Get HA by pressure on the diaphragm sella Lateral extension into cavernous sinus lead to opthalmoplegia, diplopia, ptosis (dysfxn of CN 3,4,6)Bitemporal hemianopia b/c of extension on the suprasellar space Get HA by pressure on the diaphragm sella Lateral extension into cavernous sinus lead to opthalmoplegia, diplopia, ptosis (dysfxn of CN 3,4,6)

10. Types of Adenomas Lactotroph Adenoma Somatotroph Adenoma Cortiocotroph Adenoma Thyrotroph Adenoma Non functioning Adenoma Includes Gonadotroph Adenomas Pituitary Incidentaloma

11. Prolactinoma Seen in about 40% of pituitary adenomas Usually sporadic but can also be part of MENI Most are benign Presentation differs between gender and if menopausal Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED) Prolactinemia?hypogonadotripic hypogonaidsm?estrogen deficiency?osteopenia, hot flashes, vaginal dryness Prolactinemia?adrenal androgen production?weight gain, hirsuitism ?40%, 65%Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED) Prolactinemia?hypogonadotripic hypogonaidsm?estrogen deficiency?osteopenia, hot flashes, vaginal dryness Prolactinemia?adrenal androgen production?weight gain, hirsuitism ?40%, 65%

12. Presentation Premenopausal Female Prolactin ? inhibits release of GnRH ? inhibits LH and FSH ? hypogonadotrophic hypogonadism Infertility, oligomenorrhea/amenorrhea, galactorrhea Osteopenia, hot flashes, vaginal dryness Prolactin ? adrenal androgen production Hirsutism, weight gain Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED) Prolactinemia?hypogonadotripic hypogonaidsm?estrogen deficiency?osteopenia, hot flashes, vaginal dryness Excluding pregnancy, hyperprolactinemai account for 10-20% of amenorrhea Prolactinemia?adrenal androgen production?weight gain, hirsuitism Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED) Prolactinemia?hypogonadotripic hypogonaidsm?estrogen deficiency?osteopenia, hot flashes, vaginal dryness Excluding pregnancy, hyperprolactinemai account for 10-20% of amenorrhea Prolactinemia?adrenal androgen production?weight gain, hirsuitism

13. Presentation Postmenopausal Women Already hypogonadal and hypoestrogenemic Presentation usually associated with mass effect Male Prolactin ? decreased testosterone secretion Impotence, decreased libido, infertility, gynecomastia, osteopenia, rarely galactorrhea Also commonly present with symptoms of mass effect Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED) Normal gonadotropin levels, decreased sex hormone levels (no LH surge? anovulation, decreased testosterone ? ED)

14. Workup History Pregnancy, drugs, renal insufficiency Physical Chiasmal syndrome, chest wall injury, signs of hypothyroid or hypodonadism Check prolactin levels (can be checked any time of day) During reproductive years, levels >15-20 are abnormal Levels >100 associated with hypogonadism Prolactin > 250 in non-pregnant is almost always a prolactinoma With macroadenomas causing “stalk effect”, prolactin levels usually <150 Pituitary MRI

15. Treatment Mainstay of treatment is medical (in micro and macroadenomas) Dopamine agonists Bromocriptine (if plan on getting pregnant) and cabergoline SE: N/V, orthostatic hypotension, nasal congestion TSS: when medication is not tolerated or severe invasive cases Stop offending medications If not possible, can add DA, but may worsen psychiatric illness

16. Somatotroph Adenoma 3-4 cases per million persons per year Slowly progressive so often present with macroadenomas Pituitary Gigantism vs Acromegaly Based on if epiphyses of long bones are closed GH acts on the liver to stimulate secretion of IGF-1 (somatomedin C) which acts on tissues of the body Organomegaly, soft tissue and bone hypertrophy Difft based on if long bone epiphyses are fused or not If fused, get overgrowth of bones in acral areasDifft based on if long bone epiphyses are fused or not If fused, get overgrowth of bones in acral areas

17. Somatotroph Adenoma - Diagnosis History + physical HA, carpel tunnel, OSA, increased size of foot/hand/head Skin tags, spaces between teeth, prognathism, doughy hands, frontal bossing, visual field deficits, hypogonadism Labs IGF-1 levels Glucose suppression test GH suppression with oral glucose load (75g) MRI pituitary

18. Somatotroph Adenoma Treatment Goal Normalization of IGF-1 levels Suppression of GH levels with an oral glucose load Transsphenoidal surgical resection Medication – to shrink tumor size Somatostatin Analogues (Octreotide) Dopamine Agonists Radiation (can lead to hypopituitarism) GH has somatostatin receptors Can use somatostatin analogues to shrink tumor b/f surgery (TSS)GH has somatostatin receptors Can use somatostatin analogues to shrink tumor b/f surgery (TSS)

19. Somatotroph Adenoma - Complications Cardiovascular LVH, CHF, cardiomegaly Respiratory OSA, sleep disturbances Metabolic Infertility, impotence, galactorrhea Skeletal Jaw malocclusion, hypertrophy of frontal bones, OA Gastrointestinal Higher risk of developing neoplasm, colon polyps

20. Corticotroph Adenoma Secretes ACTH Causes Cushings

21. Thyrotroph Adenoma Extremely rare (0.5-1% of pituitary tumors) Present with signs + symptoms of hyperthyroidism TSH is not stimulated by thyrotropin releasing factor and TSH is not suppressed by exogenous thyroid hormone Elevated TSH and elevated thyroid hormone levels Treatment Surgery: often needed several times Medication: somatostatin analogues Radiation

22. Non functioning Pituitary Adenoma Up to 30% of pituitary adenomas Commonly present as macroadenoma with mass effect Must do full hormone work up to rule out hypersecretion Are categorized based on immunohistochemical staining Gonadotroph adenoma (80% of nonfunctioning adenomas) More common in males Present with visual complaints (from suprasellar extension compressing the optic chiasm) Rarely present with symptoms of hormonal hyperstimulation Null Cell adenomas Do not demonstrate any immunostaining Treat with TSS and radiation

23. Pituitary Incidentaloma Presentation: Often assymptomatic Rarely present with neurologic symptoms Microadenomas Check prolactin level Macroadenomas Full hormonal work up, visual field testing Treatment: Based on results of hormonal testing If no hormonal hypersecretion is found, proceed with serial pituitary imaging (at 6 mo, annually) TSS for hormonally silent macroadenomas

24. Follow up of Patient Diagnosis: Prolactinoma Only hormone hypersecretion is prolactin, no symptoms of stalk effect Non functioning adenoma with stalk effect Prolactin <250 Started on Bromocriptine Resolution of galactorrhea Prolactin levels went back to the normal range Repeat MRI shows decreased size of adenoma