Pituitary Disorders _ Parathyroid Disorders

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5/1/2015 1 APIRADEE SRIWIJITKAMOL DIVISION OF ENDOCRINOLOGY AND METABOLISM DEPARTMENT OF MEDICINE FACULTY OF MEDICINE SIRIRAJ HOSPITAL S2iriraj Board Review 2014 PITUITARY APPROACH TO PITUITARY DISORDER S2iriraj Board Review 2014 INVESTIGATION CBC, UA, Electrolyte Hormonal study FSH, LH, E2 (testosterone) (ACTH), cortisol (during stress, morning) TSH, T4 PRL Film lateral skull MRI pituitary S2iriraj Board Review 2014 FEEDBACK LOOP OF HYPOTHALAMIC-PITUITARY-AXIS AND LABORATORY INTERPRETATION Hypothalamus Pituitary Releasing hormone Stimulating hormone Thyroid hormone Corticosteroid Sex hormone Negative feedback S2iriraj Board Review 2014 CASE AM ท่านได ้รับปรึกษาเรื่อง abnormal thyroid function test จาก ICCU ผู้ป่ วยหญิงอายุ 70 ปี มาด ้วย ACS ระหว่างอยู่ใน ICCU มี tachyarrthymia เลยเจาะ TFT TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4 (0.4-4.5) แปลผลว่า ....

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Pituitary DisorderParathyroid Disorder

Transcript of Pituitary Disorders _ Parathyroid Disorders

Page 1: Pituitary Disorders _ Parathyroid Disorders

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APIRADEE SRIWIJITKAMOL

DIVISION OF ENDOCRINOLOGY AND METABOLISM

DEPARTMENT OF MEDICINE

FACULTY OF MEDICINE SIRIRAJ HOSPITAL

S2iriraj Board Review 2014

PITUITARY

APPROACH TO PITUITARY DISORDER

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INVESTIGATION

CBC, UA, Electrolyte

Hormonal study

FSH, LH, E2 (testosterone)

(ACTH), cortisol (during stress, morning)

TSH, T4

PRL

Film lateral skull

MRI pituitary

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FEEDBACK LOOP OF HYPOTHALAMIC-PITUITARY-AXIS AND LABORATORY INTERPRETATION

Hypothalamus

Pituitary Releasing hormone

Stimulating hormone

Thyroid hormone Corticosteroid

Sex hormone

Negative

feedback

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CASE AM

ทา่นไดร้ับปรกึษาเรือ่ง abnormal thyroid function

test จาก ICCU

ผูป่้วยหญงิอาย ุ70 ปี มาดว้ย ACS ระหวา่งอยูใ่น

ICCU ม ีtachyarrthymia เลยเจาะ TFT

TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4

(0.4-4.5)

แปลผลว่า ....

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HYPOTHALAMIC-PITUITARY AXIS CHANGE FOLLOWING PITUITARY LESION

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CASE AM

ทา่นไดร้ับปรกึษาเรือ่ง abnormal thyroid function

test จาก ICCU

ผูป่้วยหญงิอาย ุ70 ปี มาดว้ย ACS ระหวา่งอยูใ่น

ICCU ม ีtachyarrthymia เลยเจาะ TFT

TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4

(0.4-4.5)

แปลผลว่า

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PITUITARY VS. NON-PITUITARY TUMOR FILM LATERAL SKULL

Anterior clinoid process

Posterior clinoid process

Floor of sella

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SELLA ENLARGEMENT

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TREATMENT

Hormone replacement

Glucocorticoid

Thyroid

Sex hormone

+GH

Treatment of underlying disease

Advice

Glucocorticoid before thyroid replacement

Glucocorticoid during stress

APPROACH TO PITUITARY DISORDER

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ACROMEGALY

Vital signs: BP

Weight, Height

Typical face:

Frontal bossing

Prognathism

Macroglossia

Coarse faces

Thickening of the nose

Cutis vertices gyrate

Thyroid gland: enlarged, MNG

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Skin: skin tags, Oily skin,

acanthosis nigrican

Wide and spread hands.

Carpal tunnel syndrome

Heart: Cardiomegaly

Abd: Hepatomegaly

Nervous system:

VF

Osteoarthritis

Galactorrhea

ACROMEGALY

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FILM FOOT

Heel pad sign

distance between the

plantar aspect of the

calcaneus and skin

surface

normal distance is 21 mm

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Lateral radiograph of skull reveals

Enlarged sella with double flooring

Dilatation of air sinus

Prognathism

Thickened skull vault

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FILM SKULL

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FILM HAND

Ungal tufting

Widening of the bases of

distal phalanges

Metacarpal osteophytes on

radial aspect (metacarpal

hooks)

Soft tissue hypertrophy

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DIAGNOSIS

IGF-1

Screening test

Higher than same age

75 g OGTT

GH > 1 ug/L

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TREATMENT

Goal

GH < 1ug/L

Normalized IGF-1

Modalities

Surgery

Medication

Dopamine agonist

Somatostatin analog

Radiation

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INDICATION FOR MEDICATION

Failed to control biochemical by surgery alone

Primary medical therapy

Patient refuse surgery

Severe cardio- or respiratory disease

Lack of experienced surgeon

Low probability of surgical cure (without

compressive symptoms)

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ADVERSE EVENTS OF SRL

Increased incidence of gallbladder sludge and

gallstone formation,

Abdominal bloating and cramping or

constipation

Bradycardia

Worsening of glucose metabolism

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APPROACH TO PITUITARY DISORDER

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CASE PS

A 23-year-old woman presented with secondary

amenorrhea for 7 months. She had no other

complaints. Physical examination revealed few

drops of milk discharge on squeezing. Otherwise

were within normal limit. Progressterone challenge

test -, FSH 1.0, LH 0.8, E2 <5.

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Galactorrhea?

Cause of galactorrhea?

Need treatment?

APPROACH TO GALACTORRHEA GALACTORRHEA

Microscopy shows fat globules in discharge.

DEFINITION

A milk-like secretion from the

breast in the

absence of parturition or

beyond 6 months’

postpartum in a

nonbreastfeeding woman

(American family physician 2004;70:543-50)

> 2 years from the last breast

feeding

(American family physician 2001;63:1763-70)

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Identify Cause

Drug use

Pituitary function

VF and VA

Hypothyroidism

CKD

Galactorhea?

Signs of hypothyroidism

Signs of hypopituitarism

VF and VA

APPROACH TO GALACTORRHEA

HISTORY PHYSICAL EXAMINATION

Etiology Mechanism Prolactin

level

Drugs -Effects on dopamine level-function -

Pituitary, stalk,

hypothalamic -Production

-Prolactin inhibitory factor -

Thyroid disease -Hypo TRH

-Hyper free estrogen

CKD -Renal clearance

-Medication: methyldopa

Neurologic

cause

-Nipple or breast stimuli

-Chest wall irritation intercostal N.

Post column Hypothalamus PIF

Idiopathic -Sensitivity to prolactin levels

-More bioactivity, low immunoactivity

CAUSES OF GALACTORRHEA

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MECHANISM DRUGS

Dopamine-receptor blockade

Metoclopramide Phenothiazines Risperidone SSRI: fluoxitine, setraline Tricyclic antidepressants

Dopamine-depleting agents Methyldopa Reserpine

Inhibition of dopamine release Heroin Morphine

Histamine-receptor blockade Cimetidine

Stimulation of lactotrophs Oral contraceptives Verapamil

DRUG-INDUCED GALACTORRHEA

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Identify Cause

Drug use

Pituitary function

VF and VA

Hypothyroidism

CKD

Assess need to treatment Menstruation Amount of galactorrhea

Galactorhea?

Signs of hypothyroidism

Signs of hypopituitarism

VF and VA

APPROACH TO GALACTORRHEA

HISTORY PHYSICAL EXAMINATION

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Hx and PE

In case, Hx of drug:

stop medication

for 3 days

PROLACTIN MEASUREMENT

•NPO 6 hours, no stress, no breast stimulation

•When in doubt, sampling can be repeated on a different day

at 15- to 20-min intervals to account for possible prolactin

pulsatility

•When there is a discrepancy between clinical and prolactin level,

serial dilution of serum samples to eliminate an artifact with some

immunoradiometric assays (“hook effect”)

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Hx and PE

In case, Hx of drug:

stop medication

for 3 days

Kidney X

Thyroid ✓

Prolactin

Kidney ✓

Thyroid X

Prolactin

Kidney ✓

Thyroid ✓

Prolactin

Kidney ✓

Thyroid ✓

Prolactin ✓

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CASE PS

A 23-year-old woman presented with secondary

amenorrhea for 7 months. She had no other

complaints. Physical examination revealed few

drops of milk discharge on squeezing. Otherwise

were within normal limit. Progressterone challenge

test -, FSH 1.0, LH 0.8, E2 <5. Her serum prolactin

is 104 ng/mL, serum TSH 1.0 mIu/L. MRI of pituitary

gland showed pituitary tumor size 0.8 cm.

DIAGNOSIS: ………….

SERUM PROLACTIN LEVEL IN 226 PATIENTS WITH

HISTOLOGICALLY VERIFIED NON‐FUNCTIONING

PITUITARY MACROADENOMA

Karavitaki N. Clinical Endocrinology 2006;65; 524-529.

Serum PRL in all patients Serum PRL in patients not taking drugs

>141.5

94.3-141.5 <94.3

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CASE PS

A 23-year-old woman presented with secondary

amenorrhea for 7 months. She had no other

complaints. Physical examination revealed few

drops of milk discharge on squeezing. Otherwise

were within normal limit. Progressterone challenge

test -, FSH 1.0, LH 0.8, E2 <5. Her serum prolactin

is 104 ng/mL, serum TSH 1.0 mIu/L. MRI of pituitary

gland showed pituitary tumor size 0.8 cm.

DIAGNOSIS: ………….

TREATMENT: ……………

abnormal

abnormal

<6 mm 6-9 mm

Freda PU. J Clin Endocrinol Metab 96: 894–904, 2011

normal

APPROACH TO PITUITARY INCIDENTALOMA

APIRADEE SRIWIJITKAMOL

DIVISION OF ENDOCRINOLOGY AND METABOLISM

DEPARTMENT OF MEDICINE

FACULTY OF MEDICINE SIRIRAJ HOSPITAL

S2iriraj Board Review 2014

CALCIUM

HOMEOSTASIS

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VITAMIN D PATHWAY

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APPROACH TO HYPERCALCEMIA

-Hyper PTH

-Lithium

-Familial hypocalciuric

hypercalcemia

-Vitamin D intake

-Granulomatous

disease

-Malignancy

- PTHrP:

- Sq cell CA

- Breast, lymphoma

- Humoral: NHL

- LOF: MM, Breast

-Endocrine dis.

-Drugs: vit A, thiazide

-Others

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TREATMENT OF HYPERCALCEMIA

Mild Moderate Severe

Symptom - - + -/+

Identify cause ✔ ✔ ✔ ✔

Supportive ✔ ✔

IV fluid*

I/O > 3L/D

✔ ✔

IV Furosemide ✔ ✔

Bisphosphanate** ✔

Calcitonin*** ✔

Hemodialysis ✔

* Be careful in elderly and heart disease patients

** Do not use in patient with acute kidney injury

*** A few days of treatment

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APPROACH TO HYPOCALCEMIA

-Low PTH:

- Hypoparathyroidism

-Low Mg

-PTH resistance

- Pseudohypo PTH

-Critical illness - Hyperphos.

- Rhabodmyolysis - Tumor lysis synd - Phosphate Rx

- Others: -Drugs:

- P450: INH, rifam, anticonvulsant ,gllucocorticoid

- Citrate

-Vit D def.

- Malabsorption

- Liver and renal

- Anticonvulsant - Elderly

-Vit D resistance

- Ricket type II

- Phenytoin Rx

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METABOLIC BONE DISEASES

Mineralization

Osteomalacia/rickets

Low bone mineral content

Osteoporosis

High bone turnover

Hyperparathyroidism

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Inadequate MINERALIZATION of normal

osteoid tissue

Different expressions of the same disease

Rickets

Areas of endochondral growth

Osteomalacia

All skeleton is incompletely calcified

OSTEOMALACIA

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Symptoms and Signs

Bone pain, backache

Muscle weakness

Vertebral collapse

Kyphosis

loss of height

Deformities & stress fractures

OSTEOMALACIA

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Bone pain Pathological fracture

•Generalized muscle weakness •Disability

Metabolic Bone Disease Others

Metastasis bone

Hematologic: MM

Rheumato

Osteoporosis

Osteomalacia

Paget’s

Osteomalacia

Pain, muscle weakness

Ca ↓, P ↓, Alk ↑

Osteopenia, looser zone

Decrease

Osteoporosos

-

-

Osteopenia

Decrease

Clinical

Lab

X-ray

BMD

Bone pain Pathological fracture

•Generalized muscle weakness •Disability

Metabolic Bone Disease Others

Metastasis bone

Hematologic: MM

Rheumato

Osteoporosis

Osteomalacia

Paget’s

Vit D def. Fanconi’s

-RTA

-Glycosuria -hypophosphatemia

Hereditary Hypophosphatemia

TIO

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Defect in Vitamin D metabolism

Nutritional

Underexposure to sunlight

Intestinal malabsorption

Liver & kidney diseases

Anticonvulsant use

Hypophosphataemia with renal phosphate wasting

RTA

Tumor-induced ostemalacia

Hereditary hypophosphatemic osteomalacia

OSTEOMALACIA

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Investigation

Blood chemistries

Calcium, Phosphate, Albumin, Alkaline

phosphatase

Renal function and E’lyte

25-OH vitamin D

iPTH

Urine calcium/phosphate

Film bone survey

Bone biopsy

OSTEOMALACIA

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PSEUDOFRACTURE

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PSEUDOFRACTURE

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PSEUDOFRACTURE

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HYPOPHOSPHATEMIA VS. VITAMIN D DEFICEINCY

*Urine phosphate > 100 mg/D , FE phosphate > 5% = high

Hypophosphatemic

Osteomalacia

Vit. D Deficiency

Osteomalacia

Calcium Normal Normal. (Low)

Phosphate Low Low

ALP High High

E’lyte In RTA -

25-OH vitamin D Normal Low

iPTH Normal, Nornal, (High)

Urine phosphate High Normal

PRIMARY HYPERPARATHYROIDISM

History

Asymptomatic

50% of symptomatic:

Renal calculi

Bone pain or fracture

Other symptoms

PU, Pancreatitis

Neuromuscular and

Neuropsychiatric

Endocrine syndrome:

MEN I or MEN IIa

Physical examination

Neck mass

Basic lab

CBC, UA

Ca, P, Alk, Alb

Electrolyte, BUN, Cr

Special test

Bone survey

BMD

MIBI scan

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Film HAND

Acro-osteolysis

Generalized

osteopenia

Subperiosteal

resorption of the radial

aspect of the middle

phalanges of index and

middle fingers

A: Subperiosteal distal clavicular resorption

B: Brown tumor, the osseous expansion

and lucency of the proximal humerus

FILM BONE SURVEY

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FILM SKULL

Trabecular bone resorption resulting in the salt-and-pepper appearance

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Brown tumor

Loss of lamina dura

FILM SKULL

Characteristic endplate

sclerosis

Rugger-jersey spine

RENAL OSTEODYSTROPHY

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Multifocal, large, amorphous

calcific deposits

Tumoral calcinosis

RENAL OSTEODYSTROPHY

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RECOMMENDATIONS FOR THE

EVALUATION OF ASYMPTOMATIC PHPT

Biochemistry panel

Ca, P, ALP, BUN, Cr, 25(OH)D

PTH level

BMD by DXA

Lumbar spine, hip, and distal 1/3 radius

Vertebral spine X-ray or VFA by DXA

24-h urine for:

Ca, Cr, CCr

Stone risk profile esp. Ur Ca >400 mg/D

Abdominal imaging by x-ray, ultrasound, or CT scan

Bilezikian et al,. J Clin Endocrinol Metab, October 2014, 99(10):3561–3569

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Symptomatic: surgery

Asymptomatic: ?Indication

PRIMARY HYPERPARATHYROIDISM

Measurement 1990 2002 2008 2013

Serum Ca

(>upper NL)

1-1.6 mg/dl 1 mg/dl 1 mg/dl 1 mg/dl

Renal

24-h Ur Ca >400 mg/D >400 mg/D -

Ccr by 30% by 30% < 60 mL/min < 60 mL/min

Others Ca-stone

risk

Skeletal

BMD Z-score <-2.0 in

forearm

T-score <-2.5 at

any site

T-score <-2.0 at

any site*

T-score <-2.5 at

any site*

Others Vertebral #

Age <50 <50 <50 <50

*Z-score in premenopausal women and in men under 50