R3 Endocrine disorders

Taweesak Wannachalee, MD

4th May 2019

Case presentation

• ผ ปวย หญงไทย ค อาย 45 ป โดยมอาการ มอสน ใจสน น าหนกลด 3 เดอน ตรวจเลอดเพมเตม พบ

T3 575 ng/dL (80-200)

FT4 5.3 ng/dL (0.93-1.7)

TSH <0.0001 uIU/mL (0.27-4.2)

• PE: HR 110/min regular, tremor positive

No lid lag, No lid retraction, No exophthalmos

No pretibial myxedema

CVS: no murmur

Case presentation

• PE:

• ขณะนรกษาโดยทานยา methimazole 15 mg, propranolol 60 mg มา 3 วน

• จงใหการซกประวต ตรวจรางกายและสงตรวจเพมเตม เพอใหไดการวนจยรวมทงวางแผนการรกษาในผ ปวยรายน

Definition

ThyrotoxicosisA clinical syndrome of hypermetabolism that results from increased serum concentrations of free T4, free T3 or both

HyperthyroidismA form of thyrotoxicosis due to inappropriately high synthesis and secretion of thyroid hormone(s) by the thyroid gland

AACE, Endocr Pract. 2011

Causes of thyrotoxicosis

Thyrotoxicosis with hyperthyroidism (High RAIU)

• Graves’ disease (60-90%)

• Toxic multinodular goiter

• Toxic adenoma

• TSH-producing pituitary adenoma

Thyrotoxicosis without hyperthyroidism (Low RAIU)

• Thyroiditis

• Thyrotoxicosis factitia

• Ectopic thyroid tissue (Low RAIU at neck)

Struma ovarii, Substernal thyroid goiter

AACE, Endocr Pract. 2011

Clinical manifestation of thyrotoxicosis

Symptoms

⚫ Hyperactivity

⚫ Tremor

⚫ Palpitations

⚫ Weight loss

⚫ Increased appetite

⚫ Heat intolerance

⚫ Menstrual disturbances

⚫ Weakness

Signs

⚫ Hyperactivity

⚫ Tremor

⚫ Tachycardia

⚫ Systolic HTN

⚫ Warm, moist, smooth skin

⚫ Hyperreflexia

⚫ Stare and eyelid retraction

⚫ Weakness

Hyperthyroidism⚫ Vital signs: BP, Pulse rate and rhythm

⚫ Body weight

⚫ GA: hyperactive tremor

⚫ Skin hair nail : fine and moist skin

Acropachy, onycholysis

Hyperthyroidism⚫ Skin hair nail : Dermopathy, vitiligo

Pretibial myxedema

Hyperthyroidism⚫ Eye signs in thyrotoxicosis

⚫Graves’ophthalmopathy (GO)

Accumulation of hyaluronic acid chondroitin sulfate and

lymphocytic infiltratation

Spare tendon

Eye signs in thyrotoxicosis

Exophthalmos Lid retraction Lid lag

Graves’ophthamopathy

⚫ Exophthalmos

Hyperthyroidism

⚫ Eye signs in thyrotoxicosis

⚫Graves’ophthalmopathy (GO)

✓Exophthalmos

✓Lid lag and retraction

✓EOM

✓Puffy and redness of eyelid, conjunctiva

Hyperthyroidism

⚫ Thyroid: size, surface, consistency, nodule, bruit, tenderness, mobility, pamberton’s sign : if lower pole can’t be palpated

⚫ Heart: Loud P2,PSM at apex

⚫ NS: Proximal muscle weakness, Reflex

Specific sign for Graves’disease

Graves’

ophthalmopathy

Graves’

dermopathy

Graves’

acropachy

Thyroid

bruit

Hyperthyroidism

Abnormal liver function test

CVS manfestations

Muscle weakness

Hyperthyroidism per se

Valvular lesion Thyrotoxicmyopathy

Complications of hyperthyroidism

Cardiomyopathy Thyrotoxic periodic paralysis

Associated with other autoimmune

diseases

Means-Lermanscratch

Associated with other autoimmune diseases : MG, PM

Associated with drug treatment

Arrhythmia

Previous liver diseases

Pulmonary HT

Symptoms and signs of thyrotoxicosis

FT3,FT4

TSH

Thyrotoxicosiswith

hyperthyroidism

Thyrotoxicosiswithout

hyperthyroidism

TSH

• TSHoma• Resistant to thyroid

hormone

• Graves’ disease• Toxic multinodular

goiter (MNG)• Toxic adenoma

• Thyroiditis• Thyroxine ingestion

Thyrotoxicosis with or without hyperthyroidism

Duration Goiter RAIU Serum Tg

With hyperthyroidism

Graves’disease > 3 months Diffuse/No High High

Toxic MNG > 3 months Multiple nodules

Normal to high

High

Toxic adenoma > 3 months Single nodule Normal High

Without hyperthyroidism

Thyroiditis < 3 months Diffuse/ firm to hard+/- pain

Low High

Exogenous T4 Variable Yes/No Low Low

Thyrotoxicosis with hyperthyroidism

Goiter Specific signs Thyroid scan TRAb

Graves’disease

Diffuse/No Ophthalmopathy

Dermopathy

Acropachy

Bruit

Positive

Toxic MNG Multiple nodules

No Negative

Toxic adenoma

Single nodule,size>3cm with

unable to

palpate other

part of thyroid

gland

No Negative

Anti TSH receptor (TRAb)

⚫ Positive 80-90% in active untreated Graves’disease

⚫ Indication for measuring TRAb

• Confirm the clinical diagnosis of Graves’disease

• Euthyroid with exophthalmos

• Pregnancy with Graves’disease

• Prognosis of pt with Graves’disease (treated with ATD)

Pathogenesis of hyperthyroidism

TRAb

Graves’disease

Stimulate growth and function

Toxic MNG

Toxic adenoma

TSH-R mutation

TSH-R mutation

Hyperthyroidism

No specific sign of

Graves’disease

Left single thyroid nodule 4 cm

Unable to palpate right side

Most likely

Toxic adenoma

GD with nodule

Thyroid scan

Rx hyperthyroidism

FNA cold nodule

Toxic adenoma

Thyroid scan

Rx hyperthyroidism

Management of hyperthyroidism

1) Antithyroid drugs

2) Ablative treatment

• Radioactive iodine ablative therapy

• Surgical ablative therapy

Management of hyperthyroidism

Initial Rx Definitive Rx

ATD

Ablative Rx

ATD

Ablative Rx

Ablative Rx

Antithyroid drugs

Methimazole(MMI; 5 mg/tab)

Propylthiouracil(PTU; 50 mg/tab)

Administration Once daily 2-3 times/day

Effect on 131I outcome No effect Decrease effect

Agranulocytosis Dose related(>30 mg/day)

Idiosyncracy

Liver injury Cholestasis Hepatocellular*liver transplantation

Transplacental passage High Low

Concentrations in breast milk

High Low

US FDA 2009 : PTU should not be used as a 1st line agent for hyperthyroidism

Antithyroid drugs

⚫Methimazole (MMI) first line agent for hyperthyroidism in adults

⚫ Propylthiouracil (PTU) preferred

• First trimester of pregnancy

• Thyroid storm

• Minor side effect from MMI

Adverse effect of anti-thyroid drugs

Minor

Common (1-5%)

• Skin reactions

• Arthralgia

• Fever

• Transient leukopenia

• Gastrointestinal

Rare

• Abnormal sense of taste or smell (MMI)

Major

Rare (0.1-0.5%)

• Agranulocytosis

• Immunoallergichepatitis

Very rare (<0.1%)

• ANCA-associated vasculitis

• Aplastic anemia

• Thrombocytopenia

• Hypoglycemia

N Engl J Med 2005;352:905-17.

Management of hyperthyroidism

Hyperthyroidism

Graves’ disease Toxic MNGToxic adenoma

Antithyroid drugsAblative therapy

Radioactive iodine RxSurgical treatment

Graves’ disease treatmentModality Considerations C/I

Antithyroiddrugs

1. Likelihood of remission (female, mild disease, small goiters, low titer TRAb)

2. High risk for Surgery3. Limit life expectancy4. Moderate to severe GO

Majoradversereactionsto ATDs

Radioactive iodine treatment

1. Contraindication to ATDs2. Plan pregnancy (>4-6 months)3. Not candidate for surgery4. Previously operated or RT at neck

PregnancyLactation

Mod/severeactive GO

Surgery 1. Large goiters >80gm2. Low RAIU3. Suspected thyroid malignancy4. Plan pregnancy (<4-6 months)5. Moderate to severe GO

CV disease end-stagecancer

ATA/AACE Guideline 2016

Management of hyperthyroidism

Hyperthyroidism

Graves’ disease Toxic MNGToxic adenoma

Antithyroid drugs Ablative therapyRadioactive iodine Rx

Surgical treatment

Graves’diseasepreferred check CBC & LFT before

start antithyroid drugs

MMI 10-30 mg/day (OD or divided dose) PTU 50-100 mg TID (divided dose)

(preferred MMI)

Clinical (BW, goiter, HR, symptoms)Biochemical (T3, FT4) status

4-6 weeks after initiation of therapy

Advice compliance and side effects

Appropriate monitoring intervals are every 4–8 weeks until euthyroid level

Clinical improve

Gradually decrease dose of ATD when clinical improve

biochemical testing and clinical evaluation q 2–3 months

Discontinue ATD after 12-18 months (T3,FT4, TSH must be normal before stop ATD)

biochemical testing and clinical evaluation q 2–3 months for 1 yr

Remission

Monitor TFT q 6-12 months

Relapsed

Ablative treatment

2nd course of ATD

Management of hyperthyroidism

Hyperthyroidism

Graves’ disease Toxic MNGToxic adenoma

Antithyroid drugsAblative therapy

Radioactive iodine RxSurgical treatment

Symptomatic treatment

Drug Dosage Frequency Considerations

Propranolol 10-40mg TID-QID • Non-selective• High dose (>160mg)

may block T4--->T3

• Preferred in nursing mother

Atenolol 25-100mg OD or BID • Relative Beta1

selective• Increased compliance

ATA/AACE Guideline 2011

Surgery

⚫ Patients should be rendered euthyroid before surgery

⚫ Near total thyroidectomy is the procedure of choice

⚫ Preoperative KI should be used before surgery (decreases thyroid blood flow and blood loss)

⚫ Complications of surgery

• Hypocalcemia <2%,

• Recurrent Laryngeal Nerve injury <1%

• Reoperation due to bleeding 0.3-0.7%

• Hypothyroid 100%

Radioactive Iodine (131I)

⚫ Extremely symptomatic or FT4 >2-3xUNL should be treated with beta-blockers (+MMI) before 131I

⚫ Usually normalize TFT and clinical within 4-8 weeks (TSH may remain suppressed for a month or longer)

⚫ Repeat 131I Rx when GD persists after 6 months or minimal response at 3 months

⚫ Lifelong annual thyroid function testing is recommended

Most likely

Toxic adenoma

Thyroid scan

FNA

Rx: ATD

Ablative Rx

Monitor SE

Pregnancy?

Case presentation 2

• ผ ปวย หญงไทย ค อาย 65 ป เปน Post I131 hypothyroidism

รกษาโดย LT4 (100 mcg) 1 tab oral OD เชา ผลเลอดอยในเกณฑปกตมาตลอด วนนมาตรวจตามนด อาการปกตด

FT4 0.6 ng/dL (0.93-1.7)

TSH 32 uIU/mL (0.27-4.2)

• จงซกประวตเพอหาสาเหตความผดปกตรวมทงวางแผนการรกษาในผ ปวยรายน

Hypothyroidism

• Treatment– Goals of treatment

• Provide resolution of the hypothyroid symptoms and signs

• Avoid overtreatment, especially in elderly

– Targets

• Primary hypothyroidism: normalized TSH and FT4

– Raise TSH target to 4-6 µIU/ml in patients aged > 70-80 yr

• Secondary hypothyroidism: FT4 in upper half of normal range

– Target may be reduced in older patients or patients with comorbidities.

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Hypothyroidism• Treatment: levothyroxine

– Factors should be considered when starting LT4

• Patient’s age

• General clinical context including presence of cardiac

disease

• Degree of TSH elevation

• Serum TSH goal

• Patient’s weight, lean body mass

• Pregnancy status

• Etiology of hypothyroidism

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Hypothyroidism

• Treatment: levothyroxine

*Not “go slow” in

– Patients rendered profoundly hypothyroid for RAI treatment

– Patients become hypothyroid after treatment of

hyperthyroidism

ATA Guidelines for Treatment of Hypothyroidism, 2014.

PopulationRecommended

initial LT4 dosage

Normal 1.6 µg/kg/day

Mild hypothyroidism (TSH ≤ 10 µIU/ml)

Subclinical hypothyroidism25-50 µg/day

Patients older than 50-60 years 25-50 µg/day

Patients with known CAD12.5-25 µg/day

start low, go slow*

Hypothyroidism

• Treatment: levothyroxine

– Administration

• Co-administration with food impairs absorption.

– 60 minutes before breakfast or 3 hour after dinner

• 4-hour separation from interfering medications

– Drugs: Ca carbonate, FeSO4 , PPI, bile acid

sequestrants, phosphate binders, aluminum hydroxide,

sucralfate

• Diseases affecting LT4 absorption: H pylori related

gastritis, atrophic gastritis, celiac disease

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Hypothyroidism

• Treatment: levothyroxine

– Diseases or medications affecting LT4 metabolism

• Increased conjugation with glucuronates and sulfates:

phenobarbital, carbamazepine, phenytoin, rifampin,

sertraline, imatinib

• Activation of D3: Tyrosine kinase inhibitors – imatinib,

metasanib, sorafenib, sunitinib, vandetanib

• Increased peripheral deiodination of T4: growth

hormone therapy

• Overexpression of D3 (consumptive hypothyroidism):

hemangioma, vascular tumor, fibroblastic tumor, GIST

• Increased TBG: estrogen

• Decreased TBG: androgen

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Hypothyroidism

• Treatment: levothyroxine

– Follow-up: TSH and FT4 (only FT4 in central hypothyroidism) at

4-6 weeks after start or adjust dose of LT4

• Dose adjustment of LT4: 12.5-25 µg/day up or down in

patients with TSH high or low, respectively.

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Patients taking levothyroxine > 200 µg/day:

check compliance

Hypothyroidism– A 45 year-old women with primary hypothyroidism from

total thyroidectomy came to your office for routine follow-up. She had no hypothyroid symptoms. Her medication was levothyroxine 100 µg/day. Her TFT was as the following.

– What is the most appropriate management?

TSH

(0.27-4.2

mIU/L)

FT4

(0.9-1.7 ng/ml)Management

2.1 1.3

8.3 1.0

25.2 0.7

3.4 1.9

12 1.8

Hypothyroidism– A 45 year-old women with primary hypothyroidism from

total thyroidectomy came to your office for routine follow-up. She had no hypothyroid symptoms. Her medication was levothyroxine 100 µg/day. Her TFT was as the following.

– What is the most appropriate management?

TSH

(0.27-4.2 mIU/L)

FT4

(0.9-1.7 ng/ml)Management

2.1 1.3 • Continue LT4 100 µg/day

8.3 1.0• Check compliance, drug interaction

• Add LT4 12.5-25 µg/day

25.2 0.7• Check compliance, drug interaction

• Add LT4 12.5-25 µg/day

3.4 1.9 • Avoid taking LT4 on the day of the test

12 1.8

• Check compliance, drug interaction

• Add LT4 12.5-25 µg/day

• Avoid taking LT4 on the day of the test

Hypothyroidism

• Treatment: levothyroxine

– Adverse effects

• Overtreatment

– Atrial fibrillation

– Osteoporosis

• Inadequate treatment

– Dyslipidemia

– Progression of atherosclerotic cardiovascular disease

– Congestive heart failure

ATA Guidelines for Treatment of Hypothyroidism, 2014.

Case presentation 2

• ผ ปวย หญงไทย ค อาย 65 ป เปน Post I131 hypothyroidism

รกษาโดย LT4 (100 mcg) 1 tab oral OD เชา ผลเลอดอยในเกณฑปกตมาตลอด วนนมาตรวจตามนด อาการปกตด

FT4 0.6 ng/dL (0.93-1.7)

TSH 32 uIU/mL (0.27-4.2)

• จงซกประวตเพอหาสาเหตความผดปกตรวมทงวางแผนการรกษาในผ ปวยรายน Adherence, Drug-interaction

Disease (malabsorption)

Time of administration

Case presentation 3

• ผ ปวย ชายไทย ค อาย 65 ป เปน Post transphenoidal Sx

hypopituitarism, OA knee

รกษาโดย LT4 100 mcg, prednisolone 5 mg

ม plan TKA วนพรงน ทาง surgeon ไดตรวจเลอด pre-operation

Case presentation 3

จงใหการวางแผน pre-operative

hormonal treatment and

post-operative treatment

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

50 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

FT4 0.92-1.7 ng/dl 0.87

TSH 0.27-4.20 uIU/mL

3.5

Normal electrolyte

Pre-operative evaluation

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

50 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

FT4 0.92-1.7 ng/dl 0.87

TSH 0.27-4.20 uIU/mL

3.5

Chronic 2 AI

Management

• Long term replacement therapy

• Glucocorticoid replacement

• Mineralocorticoid replacement (only in primary AI)

• Adrenal androgen replacement

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

Management

Long term replacement therapy

• Glucocorticoid replacement

- Hydrocortisone 15-25 mg/d in two or three divided dose

- Prednisolone 3-5 mg/d (alternatives)

- Dexamethasone is not recommended.

Clinical monitoring: well-being, BW, PR, BP, edema

– Over-replacement: weight gain, insomnia, peripheral

edema

– Under-replacement: nausea, poor appetite, weight loss,

lethargy, hyperpigmentation

Biochemical monitoring: not recommended

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

Management

Long term replacement therapy

• Mineralocorticoid replacement

- Fludrocortisone 0.05-0.2 mg/d once in the morning

- Liberal salt intake

• Clinical monitoring: salt-craving, light-headedness,

BP in sitting and standing position, peripheral edema

• Biochemical monitoring:

– Electrolyte: normal range

– PRA: upper reference range

• DHEA replacement: in female patients with low libido,

depressive symptoms or low energy level

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

Management

• Prevention of adrenal crisis

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

Conditions Suggested action

Minor procedures:

LA, most radiologic

studies

• No extra supplementation is needed.

Moderately stressful

procedures:

Ba enema, endoscopy,

arteriography

• Hydrocortisone 100 mg IV before the procedure

Major surgery:

GA, trauma, delivery

• Hydrocortisone 100 mg IV before the procedure

then 200 mg IV drip in 24 hr (50 mg IV/IM q 6

hr)

• Taper dose rapidly to maintenance dose

by half every day

Management

• Prevention of adrenal crisis

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

Conditions Suggested action

Home management

of illness with fever

• BT > 38oC: doubled dose of GC

• BT > 39oC: tripled dose of GC

• Increased consumption of electrolyte-containing fluid

as tolerated (primary AI)

• Contact physician if illness worsens or persists

for ≥ 3 days or if vomiting develops

Unable to tolerate

oral meds due to

gastroenteritis or

trauma

• Hydrocortisone 100 mg IM or SC

Moderate illness • Hydrocortisone 50 mg IV/PO BID

• Taper rapidly to maintenance dose as pt recovers

Severe illness • Hydrocortisone 100 mg IV q 8 hr

• Taper to maintenance level by half every day

Management• Prevention of adrenal crisis

Melmed S, et al. Williams textbook of endocrinology: 13th edition, 2016.Endocrine Society CPG Diagnosis and Treatment of Primary Adrenal Insufficiency, 2015.

They need to understand

✓ the importance of life-long replacement therapy

✓ the need to increase the usual glucocorticoid dose

during stress

✓ the need to notify medical staff if the patients are to

undergo any surgical procedure

Education of the patient and his or her family

✓Patients should carry a medical alert bracelet and a card

stating that they are on long-term steroid treatment

Pre-operative evaluation

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

50 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

FT4 0.92-1.7 ng/dl 0.87

TSH 0.27-4.20 uIU/mL

3.5

No testing

HC 300 mg/d

Hypothyroidism and Surgical risk

• Greater risk in overt hypothyroidism

• Risk for

- Hypoventilation

- Prolonged intubation

- Decreased drug metabolism

- Electrolyte imbalance

- Bleeding disorders

Pre-operative evaluation

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

50 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

FT4 0.92-1.7 ng/dl 0.87

TSH 0.27-4.20 uIU/mL

3.5

No testing

HC 300 mg/d

Go on surgery

+/- increase LT4 dosage

Acknowledgement : My family &

Endocrine oncology and

adrenal team

Prof. Richard J Auchus

Prof. William E Rainey

Assist. Prof. Adina F Turcu

Assist. Prof. Tobias Else

M 35 Y : Acromegalic features

Film skullSella view

IGF-1 = 212 ng/mL (90-250)IGF-1 = 1526 ng/mL (82-160)

M 35 Y : Acromegalic features

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

1526 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

T4 5.1-14.1 mcg/dl

7.37

TSH 0.27-4.20 uIU/mL

3.5

140

Differential diagnosis

✓ Stalk effect✓Co-secretion

Prolactin level

Serial dilution of samples

Dopamine

Especially inPitu macroadenoma

Dopamine = prolactin inhibiting factor

PRL

STALK EFFECT

HOOK EFFECT

M 35 Y : Acromegalic features

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

1526 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

T4 5.1-14.1 mcg/dl

7.37

TSH 0.27-4.20 uIU/mL

3.5

Hypogonadotrophichypogonadism

2.45

3.3

M 35 Y : Acromegalic features

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

1526 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 110.9

T4 5.1-14.1 mcg/dl

7.37

TSH 0.27-4.20 uIU/mL

3.5

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

1) 8 am. Basal serum cortisol

Diurnal variation

Drug interference :WithdrawalHydrocortisone 24 hrPrednisolone 3 daysDexamethasone 5 days

Non-Emergency setting

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

1) 8 am. Basal serum cortisol

Interpretation:

<3 µg/dL strongly suggest adrenal insuff

>14.5 µg/dL intact HPA axis

Caution: Cortisol binding globulin

CBG cortisolex. Pills

CBG cortisolex. Hypoalbuminemia

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

2) 250 µg ACTH stimulation test

Serum cortisol0 min

250 µg ACTH IV

Serum cortisol30 min

Serum cortisol60 min

✓ The test can be performed without time constraints✓ this test can’t differentiate type of adrenal insuff

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

2) 250 µg ACTH stimulation test

Interpretation:

Peak cortisol >18 µg/dL intact HPA axis

Caution: Recent secondary adrenal insuff

✓ the adrenal cortex might still respond to exogenous corticotropin administration adequately

Serum cortisol0 min

Serum cortisol20 min

Serum cortisol30 min

Serum cortisol40 min

1 µg ACTH IV

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

3) Insulin tolerance test (ITT)

Basis : Counterregulatory hormones

HYPOGLYCEMIA

Severe stress✓ Hypoglycemia✓ Shock✓ High grade fever

cortisol >18 µg/dL

Diagnosis of adrenal insufficiency

To confirm inappropriately low cortisol secretion

3) Insulin tolerance test (ITT)

Interpretation: When hypoglycemia (BS<40)

cortisol >18 µg/dL intact HPA axis

Caution: High risk for patient with

✓ Cardiovascular disease

✓ Seizure

Diagnosis of adrenal insufficiency

To find out whether the adrenal insufficiency is primary or central

Basal ACTH level

ACTH level > 100 pg/mL ACTH level normal or low

M 35 Y : Acromegalic features

Hormone Reference Result

IGF1 82.9-160.9 ng/ml

1526 ng/ml

Prolactin 1.79-23.3 ng/ml

15

Testosterone 2.73-8.16 ng/ml

1.05

LH 1.7-8.6 mIU/ml

0.02

FSH 1.5-12.4 mIU/ml

0.62

Morning cortisol

6.2-19.4 mcg/dl

6.5

T3 80-200 ng/dl 50

T4 5.1-14.1 mcg/dl

2.4

TSH 0.27-4.20 uIU/mL

0.5

110

2.5

6

Evaluation of thyroid function

T3, freeT3 T4, freeT4 TSH

Primary hypothyroidism

TSH

T3 and T4

Evaluation of thyroid function

T3, freeT3 T4, freeT4 TSH

Normal

Secondaryhypothyroidism

TSH

T3 and T4

Causes of hypothyroidism

Primary hypothyroidism

Secondary hypothyroidism

Chronic autoimmune thyroiditis

Pituitary diseases

Post I131 treatment Hypothalamic diseases

Post subtotal and total thyroidectomy

Iodine deficiency

Drugs with antithyroidaction

Infiltrative disease of thyroid

History & PE

Anti TgAnti TPO

VF defectOther pituitary hormones

MRI pituitary

M 35 Y : Acromegalic features

Pituitary tumour in younger patients

Final diagnosis :

Acromegaly from pituitary

macroadenoma

Multiple Endocrine Neoplasia

MEN 1 MEN 2A MEN 2B

Acknowledgement : My family &

Endocrine oncology and

adrenal team

Prof. Richard J Auchus

Prof. William E Rainey

Assist. Prof. Adina F Turcu

Assist. Prof. Tobias Else