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ENDOCRINE CONUNDRUMS

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A 57 year old woman comes to clinic complaining of progressive fatigue. ... Acromegaly. Hypercortisolism. Insulin Resistance. Pheochromocytoma. Hyperaldosteronism ... – PowerPoint PPT presentation

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Title: ENDOCRINE CONUNDRUMS


1
ENDOCRINE CONUNDRUMS
  • Robert E. Jones, MD, FACP, FACE
  • Professor of Medicine
  • University of Utah

2
Cases
  • An unusual case of hypothyroidism
  • When is hypertension secondary?
  • Hypercalcemia in an elderly woman
  • Edema and weakness in a septagenarian

3
Hypothyroidism
4
Case 1
  • A 57 year old woman comes to clinic complaining
    of progressive fatigue. She describes it as
    beyond exhaustion. Her past medical history
    has been relatively unremarkable, and she is not
    on any chronic medication.
  • Physical examination is unrevealing.

5
Case 1
  • Laboratory evaluation
  • CBC
  • LFTs
  • ESR
  • BMP
  • Thyroid functions
  • TSH 0.4 uU/mL (normal 0.4-4.0)
  • Free T4 0.6 ng/mL (normal 0.8-1.8)
  • What does this represent?

Normal
6
Hypothalamic-Pituitary-Thyroid Axis
Primary Hypothyroidism Lack of T4/T3 feedback
results in increased secretion of TRH and TSH.
Secondary (Central) Hypothyroidism Lack of TSH
(or TRH) results in decreased thyroid
production/secretion of T4.
7
Relationship Between T4 and TSH
TSH
Normal Range
T4
8
Case 1
  • What is the differential diagnosis?

Pituitary dysfunction (any cause)
Lab error/medications
What else could this be?
Early recovery from thyroiditis
Euthyroid sick
9
Lab Error/Medications
  • An out and out goof
  • Analog determinations of free T4 tend to
    underestimate the true value
  • Elevated TBG
  • Estrogen/pregnancy
  • Binding defects
  • Phenytoin
  • Displacement
  • Heparin

10
Time Course of Thyroiditis
11
Euthyroid Sick
12
Case 1 --- Revisited
  • Directed history
  • No suggestion of a prior severe sore throat or
    hyperthyroid phase
  • Directed exam
  • Thyroid is normal no nodules
  • DTRs reveal pseudomyotonia
  • Thumbprinting is noted on the forehead
  • What further labs may help?

13
Pituitary Anatomy and Function
Reproduction LH/FSH Testosterone/Estradiol
Growth GH/IGF-1
Thyroid TSH Thyroxine
Adrenal ACTH Cortisol
Lactation Prolactin
14
Case 1---Additional Lab Tests
  • Basal pituitary evaluation
  • TSH 0.6 uU/ml (normal 0.4-4)
  • Free T4 (equilibrium dialysis) 0.4 ng/ml
    (normal 1-2.2)
  • FSH 4 uIU/ml (postmenopausal gt20)
  • Prolactin 57 ng/ml (normal lt23)
  • GH lt0.1 ng/ml (normal 0-5)
  • IGF-1 34 ng/ml (normal 75-230)
  • ACTH 12 pg/ml (normal 6-45)
  • Cortisol 7 µg/dl (normal 5-23)

15
Case 1---Summary
  • Basal lab evaluation documents
  • Secondary hypothyroidism
  • Secondary hypogonadism
  • Suspected growth hormone deficiency
  • Slightly elevated prolactin
  • Uncertain adrenal status
  • What next?

16
Case 1---Pituitary MRI
17
Case 1---What Is the Next Step?
  • Refer to a neurosurgeon
  • Refer to an endocrinologist
  • Start thyroid hormone replacement

….Not Yet! Adrenal axis must be addressed
18
Hypertension
19
Case 2
  • 46 year old man comes to clinic for a routine
    physical examination. His intake blood pressure
    is remarkable---200/110 mmHg. He is absolutely
    asymptomatic and relates that he was told his
    blood pressure was borderline over the past 5
    years. He is an accomplished skier and an avid
    outdoorsman.
  • Family history is rife with early cardiovascular
    death (sudden deaths in brother 42 and mother
    50).
  • Complete physical examination is unremarkable.

20
Case 2---Laboratory Evaluation
  • Renal function
  • Creatinine 1.0 mg/dl BUN 18 mg/dl
  • Electrolytes
  • Na 142 mEq/L K 4.3 mEq/L Ca 9.7 mg/dl
  • Urine analysis
  • No protein sediment benign

21
Case 2---Differential Diagnosis
  • Essential hypertension
  • Renovascular hypertension
  • Endocrine causes

22
Endocrine Causes Of Hypertension
  • Hyperthyroidism
  • Hypothyroidism
  • Hyperparathyroidism
  • Acromegaly
  • Hypercortisolism
  • Insulin Resistance
  • Pheochromocytoma
  • Hyperaldosteronism

23
Case 2---Evaluation
24
Differential Diagnosis
  • Adrenal cortex
  • Adenoma
  • Hyperplasia
  • Carcinoma
  • Adrenal medulla
  • Pheochromocytoma
  • Ganglioneuroma
  • Metastases
  • Lung, breast, colon, melanoma
  • Others
  • Myelolipoma
  • Hamartoma
  • Teratoma
  • Hemorrhage
  • Technical problem
  • Splenule
  • Pancreatic
  • Artifact

25
Case 2---Endocrine Evaluation
  • 24 hour urine
  • VMA 4.3 mg/d (normal 0-6)
  • Metanephrine 312 µg/d (normal lt300)
  • Normetanephrine 920 µg/d (normal lt900)

26
Case 2---MIBG Scan
27
Case 2---Endocrine Evaluation
  • 24 hour urine (repeat)
  • VMA 3.3 mg/d (normal 0-6)
  • Metanephrine 215 µg/d (normal lt300)
  • Normetanephrine 560 µg/d (normal lt900)
  • Plasma metanephrines
  • Normetanephrine 0.78 nmol/l (normal lt0.89)
  • Metanephrine 0.36 nmol/l (normal lt0.49)
  • Conclusion No biochemical evidence of a
    pheochromocytoma

28
Case 2---Further Evaluation
  • No clinical evidence of hypercortsolism
  • Is it an aldosteronoma?
  • Plasma aldosterone 20 ng/ml (normal 4-31)
  • Plasma renin activity lt0.1 ng/mg/hr
    (normal 0.5-3)
  • Adosterone/PRA ratio gtgt 25 (normal lt25)
  • Urinary aldosterone (after salt loading)
  • 10 µg/d (normal lt11)
  • After all of this, what does he have?

29
Case 2---Conclusion
  • Low renin essential hypertension and an
    incidentally discovered adrenal lesion
  • Treatment
  • Chlorthalidone 25 mg
  • Amiloride 5 mg
  • Calcium channel blocker

30
Hypercalcemia
31
Case 3
  • A 75 year old woman is referred for evaluation of
    hypercalcemia. Over the past 6-9 months, the
    family had noted a progressive decline her
    ability to function independently. On the day of
    admission, the patient was unable to walk and
    later became unresponsive. No prior history of
    hypercalcemia.
  • She was admitted with a total calcium of 17.3
    mg/dl and and albumin of 2.5 g/l.
  • Acute treatment consisted of IV hydration and
    pamidronate (90 mg IV).

32
Case 3---Differential Diagnosis
  • PTH-mediated
  • Parathyroid adenoma/hyperplasia
  • Parathyroid carcinoma
  • Ectopic PTH (paraneoplastic)
  • PTH-independent
  • PTHrp (squamous cell carcinoma, breast cancer)
  • 1,25-diOH vitamin D (sarcoidosis, lymphoma)
  • Exogenous (vitamins A or D, calcium)

33
PTH and Calcium Relationship
X
X
PTH (pg/ml)
Normal
Patient result PTH 500 pg/ml
X
X
Total Calcium (mg/dl)
34
Case 3---PTH-Mediated Hypercalcemia
35
Case 3---Physical Examination
  • General appearance
  • Elderly, frail woman. NAD. Slow mentation
  • HEENT
  • Lenticular calcifications suspected
  • Neck
  • 3X4 cm ill-defined mass in the inferior aspect of
    the left lobe
  • No associated adenopathy
  • Remainder of examination was noncontributory

36
Case 3---Further Evaluation
  • Lab
  • Total serum calcium 9.2 mg/dl
  • PTH 189 pg/ml (normal 5-65)
  • 24 hour urine calcium 233 mg/d (normal lt250)
  • ?-HCG 7.5 uIU/ml (normal lt1)
  • What do you think? What might be the next
    step(s)?
  • Neck ultrasound
  • Chest CT
  • Sestimibi scan

37
Case 3---Neck Ultrasound
38
Case 3---Chest CT
Lesion
No mediastinal adenopathy
39
Case 3---Sestamibi Scan
L
L
10 Minutes
120 Minutes
40
Case 3---Therapeutic Options
  • What are our options to manage this patient?
  • Observation
  • Surgery
  • Indications for surgery
  • Age lt 45 years
  • Symptomatic hypercalcemia (or history of life
    threatening hypercalcemia)
  • Osteoporosis
  • Marked hypercalcemia (gt11.5 mg/dl)
  • Nephrocalcinosis or kidney stones
  • 24 hour urine gt 400 mg/d
  • Unable (or not likely) to agree to continuous
    medical followup

41
Case 3---Surgical Findings
  • Parathyroid
  • Benign adenoma
  • Thyroid

Follicular carcinoma
42
Case 3---Followup
  • Placed on L-thyroxine 0.150 mg/d
  • 2 months later
  • Serum calcium 8.9 mg/dl
  • PTH 95 pg/ml (normal lt75 pg/ml)
  • TSH lt0.01 uU/ml (normal 0.3-4)
  • Free T4 1.7 pg/ml (normal 0.7-1.8)
  • Thyroglobulin lt0.2 ng/ml

43
Hypercortisolism
44
Case 4
  • 74 year old woman is seen with complaints of
    progressive peripheral edema and weakness. The
    patient noted the onset of edema 10 months ago
    and over the past 6 weeks, she has had worsening
    hypertension and facial swelling. Her 3 year
    old drivers license does suggest her face is much
    fuller (but this very subtle).
  • Cardiac evaluation (catheterization, thallium
    stress test) was negative.
  • Her current medications are Tecturna 150 mg,
    Diovan/HCT 160/25 mg, atenolol 50 mg, Lasix 20
    mg, KCl 40 mEq

45
Case 4---Physical Examination
  • VS
  • BP 156/95 mmHg pulse 68
  • General appearance
  • Slender woman in NAD. Face slightly rounded,
    flushed. No acne or hirsutism. Minimal dorsal
    fat pad
  • Bland striae on abdomen
  • 3 pretibial pitting edema

46
Case 4---Initial Laboratory
  • CBC, LFTs, UA---normal
  • 5 PM cortisol 27 µg/dl ACTH 40 pg/ml
  • K 3.2 mEq/l
  • FSH 67.8
  • Does this patient have hypercortisolism?

47
Case 4---Diurnal Pattern
48
Case 4---Hypothalamo-Pituito-Adrenal Axis (HPA)
49
Case 4---Evaluation of Hypercortisolism
50
Case 4---Hypercortisolism Differential
Based upon this information, what is your best
clinical guess?
51
Case 4---Additional Lab
  • 24 hour urinary free cortisol
  • 267 µg (normal lt50)
  • Pituitary MRI
  • Normal
  • Abdominal CT/Octreotide scan
  • Octreotide scan suggested uptake in the
    mediastinum

52
Case 4---Conclusion
  • The patient was referred for a percutaneous
    biopsy of the adrenal mass. Pathology was
    positive for a mucinous cystadenocarcinoma, and
    samples were sent for determination of CRH which
    were positive.
  • In the meantime, she was placed on ketoconazole.
    Surgery is pending.

53
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