Mark Rowan MD/PGY-2

12 yo F Doubled her weight (80 -> 160 lbs.) over a 4 month period. She eats and eats w/o ever feeling satisfied. Polydipsia and polyuria/urinary frequency Noticed a swelling in her left neck a few months ago, been gradually enlarging Intermittent low-grade fevers x1 month, but none in the last 24 hrs Hypertensive during recent outpatient evaluations. Increasing shortness of breath over the last week, mostly exertional, but over the last 2 days been c/o worsening SOB when lies flat Been sleeping progressively more upright for last couple weeks. Awakens multiple times each night short of breath. Mother notes breathing at night been getting noisier. Intermittent non-productive cough over last couple weeks Large amounts of diarrhea Intermittent pruritic rash over abdomen She was evaluated at OSH yesterday and had a CXR which per parents' report was concerning for an enlarged cardiac silhouette.

PMH: Possible seasonal allergies. No hospitalizations. >1 yr ago had an I&D of gluteal and axillary abscesses, culture +MRSA. No menarche yet. FH: Father with HTN. PGF had congestive heart failure and coronary artery disease.
SH: Lives at home with parents and two younger sisters. Attends 6th grade which she enjoys. Straight A student. She participates in school basketball and plays the viola. 1 dog and 1 cat at home.

Constitutional: + fatigue.
HEENT: no sore throat, no sinus drainage. CV: No chest pain on exertion, no palpitations. + swelling of the feet and ankles. Resp: +chest pain with deep inspiration.

GI: Loose stool and increasd flatulence. No nausea, vomiting, GI bleeding, or constipation.
GU: No dysuria or hematuria. Heme: No easy bruising or bleeding, or tender or palpable lymph nodes. Musculoskeletal: +back stiffness. No joint pain, swelling or redness, or decreased range of motion. Derm: +stretch marks, shallow and narrow. No ulcerations. Neuro: No headache, blurred vision, and no new areas of focal weakness or numbness. walking well. Psychiatric: no new mood changes

v/s: T37.5, HR140, RR30, BP118/50, Sat 95%. Ht 153cm (44%ile), Wt 72kg (99%ile) GEN: Obese preadolescent female sitting up in bed in mild respiratory distress at rest, cooperative and alert. HEENT: PERRL, EOMI, TM's clear bilaterally. No nasal discharge. OP and dentition normal. No oral lesions or exudates. NECK: supple. Palpable L neck mass in lower neck and supraclavicular region. No other cervical adenopathies. Normal thyroid gland to palpation. CV: RRR, nl S1S2. No murmur or gallop. Trace pretibial edema bilaterally. Cap refill =2 sec. RESP: Rapid shallow breathing. Good aeration without adventitious sounds. ABD: Obese centrally. Semi-firm, but non-tender, slightly distended, without fluid wave. No masses or HSM. +BS. EXT: No clubbing or cyanosis. No deformities. NEURO: Cranial nerves 2 to 12 normal. Motor tone normal, strength grossly intact though difficult to assess as patient in bed and fatigued. SKIN: Mild diffuse acne to forehead. No hirsutism, no acanthosis nigricans. Pink striae to upper thighs medially and posteriorly. GU: Tanner 3 breast development and pubic hair. No axillary hair.

Endo
Heme-Onc
Cushings T2DM Medullary thyroid carcinoma Neuroendocrine

GU
Psych CV
UTI/Pyelo Binge eating disorder CHF/pulmonary edema
Myocarditis Pericarditis Endocarditis

ID

tumor/Carcinoid syndrome Pheochromocytoma Peripheral T-cell lymphoma Paraneoplastic syndrome CAP Pertussis TB Infectious Gastroenteritis

Pulm

Obesity Hypoventilation

Other:

(Pickwickian syndr) OSA

Pregnant

Labs:

TSH, FT4, Thyroid Abs: wnl AVP: wnl FSH, LH, PRL: wnl GH: 0.08 (nl 0.05-17.3) IGF-1: wnl Celiac panel: (-) Vit D: 14 (low) Urine catecholamines & metanephines: wnl Beta hCG: neg Glc: 88

Imaging:

Bone Age = 13.6 yrs, Chron age of 12 yrs. CT neck: 3 X 3.6 cm L supraclavicular mass or conglomeration of nodes

Neck biopsy (needle x1, open x2, repeated d/t regrowth):

Grew group F strep and staph epi. Path results indefinitive initially.

Labs:

Micro

CBC: WBC 11.9 (67%N, 16%L,8%M, 5%E), Hb 11.3, Hct 35.9, plts 454 CMP: glc 143, ALT 55, AST 38 RFA: (-) ESR 41 LDH: 830 (370-785), uric acid 4.2 C dif, EHEC, Adeno 40/41: (-) HbA1C: 6.4, insulin and glucagon: wnl CBG: no CO2 retention U/A: wnl Legionella urine Ag: (-), serum Ab (-)

Imaging:

Stool cx: Yeast predominant, normal enteric flora severely restricted CXR: lingular consolidation

AFP, BhCG tumor markers: wnl CEA, Calcitonin: wnl Somatostatin: 42 (<30), Chromogranin A: 186 (<95), Gastrin 608 (<100), VIP: wnl Blood serotonin: 323 (50-200), urine 5-HIAA: wnl Plasma metanephrines, VMA & HVA urine: wnl Lipid profile: wnl Salivary cortisol: nl x1, mildly elevated x1 24 hr urine cortisol: 74 and 137 (<37) Serum cortisol: wnl x2 Dexamethasone suppression test: cortisol suppressed but inadequately. Multiple ACTH checks: wnl

Echo: small-moderate global pericardial effusion, nl size & fxn

Thyroid u/s: nl Brain MRI: minimal thickening of pituitary stalk of unknown significance, nl pituitary & hypothalamus.

Pan CT/PET scan: abnormal radionucleotide activity in lymph nodes in the left side of the neck (despite recent resection) and mediastinum, most c/w neoplasm, but non-indicative of a primary tumor site.

Though ACTH wnl it is thought she has a tumor producing a truncated ACTH molecule not detected by our assay.
Open biopsies of L neck were indefinitive, but appeared to be a malignant hematopoietic neoplasm, most consistent with a peripheral T-cell lymphoma Immunostaining of tumor cells on glass slide was mildly positive for ACTH granules when compared to control slide. Despite the lack of a clear diagnosis she was started on chemo given her progressive clinical worsening (growing pleural effusion and resp distress despite adequate antibiotic coverage) Effusion improved after initiation of chemo, mediastinal and L neck mass improving

Cushings syndr. = elevated cortisol (iatrogenic, adrenal, or ectopic) Cushings dz = pituitary adenoma causing Cushing's syndr.
Sxs:
Rapid wt gain (particularly of trunk & face), buffalo hump, moon face Hyperhidrosis (excessive sweating) Telangiectasias, thinning of skin, striae Proximal muscle weakness Hirsutism, acne Insomnia Various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common. Inhibited aromatase -> reduced libido, impotence in men, amenorrhea/oligomenorrhea and infertility in women due to elevations in androgens and negative feedback of cortisol on the hypothalamus decreasing GnRH release. Polyuria (and accompanying polydipsia) Persistent HTN (cortisol enhances epinephrine's vasoconstrictive effect) Insulin resistance (especially common in ectopic ACTH production) Hyperpigmentation (if elevated ACTH)
d/t Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Proopiomelanocortin (POMC)

Cushings
Dx: Dexamethasone suppression test vs 24 hr urine cortisol Salivary cortisol newly FDA approved If abnl
CT adrenals MRI pituitary Rarely petrosal sinus sampling needed to measure ACTH levels

Slow growing malignant tumor ~2/3 in midgut (ileum/appendix), ~1/4 in the respiratory tract, rarely ovary or thymus. ~10% secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:

Flushing Diarrhea Wheezing Abdominal cramping Peripheral edema