Endocrinology Review

By Saif Borgan M.D.Education Courses

Endocrinology Review episodes

June 05 Episode 27: Cardiovascular safety of Testosterone Replacement Therapy
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Learning objectives:
1- Identify main objective of the TRAVERSE study and be familiar with its outcomes pertaining to the primary safety end point of MACE
2- Identify other possible Adverse events associated with testosterone replacement therapy and contrast them with other systematic reviews and meta analyses already published
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6 min
March 13, 2025 Episode 26: Thyroid Storm and Thyrotoxic periodic paralysis
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Learning objectives:
1- Describe pathophysiology of Thyrotoxic periodic paralysis
2- Identify and manage thyroid storm
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8 min
January 27, 2025 Episode 25: Graves Eye Disease
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Learning objectives:
- Describe pathophysiology of Graves eye disease
- Identify scoring systems used for classification of Graves eye disease
- Discuss potential treatments used for Graves eye disease, including their side effects
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11 min
January 20, 2025 Episode 24: Graves disease
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Learning Objectives:
1- Describe the pathophysiology of Graves disease
2- Able to identify the presentation of Graves disease
3- Discuss different treatments modalities of Graves disease
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6 min
December 12, 2024Episode 23: Subclinical Hyperthyroidism
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Learning objectives:
Define subclinical hyperthyroidism
Prevalence and causes of subclinical hyperthyroidism
Clinical impacts of subclinical hyperthyroidism
Management of subclinical hyperthyroidism
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7 min
November 03, 2024Episode 22: Thyroiditis
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Episode 22: Thyroiditis
How to differentiate thyroiditis from other causes of hyperthyroidism
Phases of thyroiditis and how it can affect thyroid test results
Causes of thyroiditis, and key differences
Management of thyroiditis

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9 min
October 28, 2024 Episode 21 (edited): How to approach a high TSH
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Episode 3 Approach to high TSH

Educational objectives:
1- Approach and differential diagnosis of high TSH
2- Picking up on hidden exam question clues in high TSH scenarios
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6 min
October 21, 2024 Episode 21: Approach to a High TSH
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Endocrine Review Course Learning Objectives:
- Discuss the differential diagnosis of a High TSH
- Identify physiological mild TSH elevation with advanced age that does not require treatment
- Be able to pick up on exam question clues of high TSH scenarios

Text:
A 20-year-old female presents to her primary care physician for a wellness check. She reports fatigue and sleepiness. Family history includes hypothyroidism in her mother. Her physical exam reveals slightly enlarged thyroid gland. Her vital signs within normal reference ranges. Her TSH was measured and was elevated at 7.5. What’s the best next step:
·
Check FT4·
Start levothyroxine·
Perform thyroid US·
Check Thyroid peroxidase antibody

And the answer is Check FT4. This would be needed to confirm and characterize hypothyroidism (overt vs subclinical). Starting levothyroxine at this point is premature. Although this patient has enlarged thyroid, however thyroid ultrasound is not a routine part of hypothyroidism evaluation and would not be the best next step. While measuring TPO may help explain the etiology, it would not be the best next step. Reference range can vary widely depending on the assay measurement. With that caveat for serum TSH, normal reference range is typically between 0.4 – 4.0 mU/l. Above 2mU/l the risk of developing hypothyroidism increases especially in the presence of TPO antibodies.

When encountering high TSH, you should immediately have 3 differential categories:o
First category is Appropriate pituitary response to low levels of thyroid hormone, in this case, the pituitary is attempting to increase thyroid hormone production§ Such as in primary clinical and subclinical hypothyroidism, from Hashimoto’s, thyroid radiation, previous thyroid surgery, and drug induced hypothyroidism like amiodarone, lithium, interferon-alpha, and immune checkpoint inhibitors, TKI, physiological increase with later age, morbid obesity Second category is Inappropriate pituitary response, in this case, thyroid levels are high, but the pituitary continued to provide stimulation to the thyroid due to pituitary pathology or resistance (TSHoma or thyroid hormone resistance) which will be discussed in detail in a future episode. Briefly TSHoma or thyrotropinoma is rare TSH-secreting pituitary tumor. Thyroid hormone resistance is due to mutation in TSH receptor. This can also be seen in the late recovery phase of thyroiditis and in recovery of sick euthyroid syndrome.
Third category is lab assay abnormalities such as Macro-TSH. We previously mentioned assay interference with antibodies but also Macro-TSH can cause interference. TSH is elevated usually VERY HIGH like 100 mIU/L and thyroid hormone levels here are typically normal. Macro-TSH is a macromolecule made from the autoimmune anti-TSH immunoglobulin and TSH molecule. It is biologically inactive. The gold standard method to detect macro-TSH is chromatography. It is also important to keep in mind macro-TSH for persistent TSH elevation.

Exam Clues- In each Clinical scenario, you should screen the question for specific supportive clues, for example:o Family or personal history of autoimmune disease could support primary hypothyroidism/Hashimoto’s diseaseo Strong multigenerational Family history of thyroid disorder (autosomal dominant pattern) could support TSH resistance, genetic testing for THR-B is possibleo Recent critical illness could indicate sick euthyroid in recovery phaseo Unusual diet such as kelp/seaweed/seamoss diet or recent IV contrast may s
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8 min
September 15, 2024 Episode 20: Approach to a Low TSH
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Hello and welcome to this episode. Today we will be discussing an approach to a low TSH.

We will be going over 2 review studies from The Journal of Clinical Endocrinology and Metabolism and then Cleveland Clinic Journal of Medicine. But first today’s question:

A 50-year-old postmenopausal woman with no other notable history presenting with palpitations, frequent bowel movements, and tremors. She has no family history of thyroid dysfunction. She has mild tachycardia. Her thyroid gland is 20 g and nontender to palpation. Her TSH is < 0.1.

What is the best next step in evaluating this patient?
A Thyrotropin receptor antibodies
B Check Total T4
C Check Free T4 and T3
D Thyroid US

And the answer is T4 and Total T3. These questions, while seemingly simple, are actually guaranteed on board exams.

Initial thyroid function evaluation should start with TSH. In this case the TSH is low and there is clinical suspicion for hyperthyroidism. If TSH is suppressed, the immediate next step is to check T4 and T3 to confirm and further characterize the thyroid dysfunction (overt vs subclinical). This is worth repeating: investigating the cause of the suppressed TSH by checking thyroid hormones is important in determining how to proceed with evaluation and treatment.

In this question, checking the Free T4 is favored over total T4 because Total T4 levels can be affected by alterations in binding proteins. Checking T4 only is not sufficient because there are cases of isolated T3 thyrotoxicosis. Ordering receptor antibodies or starting treatment are premature at this point. Thyroid US is not a routine part of the diagnostic algorithm to hyperthyroidism. For this case, an iodine uptake scan could be performed to differentiate thyroiditis from true hyperthyroidism, but this would not be the best next step in this question.

An Approach to Low TSH
If the T4 and T3 level are normal, repeat TSH, T4, and T3 in 6-8 weeks before giving a diagnosis. When TSH suppression is transient, most times thyroid dysfunction will be resolved in this time. A suppressed TSH that is not normalized in this period requires more investigation.

Low TSH can be differentiated by level of TSH suppression such as mild (TSH 0.1 – 0.4 mIU/L) milli-international units per liter and complete TSH suppression TSH < 0.1 mIU/L. It is unclear the incidence of low TSH within the population but in a representative sample of the US without known thyroid condition that 0.7% of patients had suppressed TSH (< 0.1 mU/L) and 1.8% of patients had a TSH level below the reference range (< 0.4 mU/L)

It can be helpful to think of the etiologies of low TSH 1) in their relation to the pituitary/hypothalamus or 2) in terms of accuracy of the assay measurement / drug effect

Relationship to Pituitary/Hypothalamus
· Category #1: low TSH due to an appropriate pituitary response to high thyroid hormone, the pituitary is actively attempting to reduce thyroid hormone production because of advanced or early elevated thyroid hormone levels

In this category differentiating the source of the excess thyroid hormone can be helpful
· #1 Excess endogenous thyroid hormone production from multinodular goiter, autonomous thyroid nodule, Graves’ disease,
· #2 Exogenous thyroid hormone commonly from excess levothyroxine supplementation (iatrogenic or intentional in context of high risk thyroid cancer) or ingestion of natural thyroid preparations (athletic performance and integrative health) – in these cases exogenous T4 is suppressing TSH so will be characterized by low TBG
·
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8 min
September 05, 2024 Episode 19: Thyroid physiology and Deiodinase enzymes
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Endocrine Review Course Learning Objectives:
- Discuss thyroid hormone axis
- Discuss how thyroid hormone is produced
- Discuss the differences between T4 and T3
- Discuss the types of diodinase enzyme
- Discuss how thyroid hormone enters the cell
- List actions of thyroid hormone (on a molecular level)

TRANSCRIPT
Hello, my name is Kristen Lee and I am an Endocrinology fellow at Northwestern University in Chicago, Illinois. I am joining the Endocrine Review team and hope to help my colleagues pass the endocrine boards!

Todays question is: which of the diodinase enzymes is most active in illness?
Diodinase 1, 2 , 3 or 4.

And the Answer is Diodinase THREE

======

The learning objectives today:
In order to better understand and interpret thyroid laboratory findings we first need to take a step back and discuss the thyroid hormone regulatory pathway.

In particular the thyroid hormone axis
Starting at the hypothalamus, thyrotropin-releasing hormone (TRH) induces the pituitary to secrete thyroid stimulating hormone (TSH). TRH interacts with the thyrotrophic cell receptor to influence TSH glycoclysation which informs TSH bioactivity.

TSH production is made in a pulsatile circadian fashion with its peak between 2am-4am (referred to as the nocturnal TSH surge) and its trough between 4p and 8p. In a euthyroid human, TSH is produced at between 50-200 milliunits/day and can increase to up to > 4000 mU/day in primary hypothyroidism. The half-life of TSH is betwee n 50 and 80 minutes. TSH bioactivity changes based on TSH glycosylation variability; due to different glycosylation nocturnal TSH is less bioactive which is why TSH does not lead to increased thyroid hormone production at night.

After TSH production, T SH binds to thyroid releasing hormone receptors on the thyroid follicular cells activating the thyroid synthesis cascade.

The Thyroid Synthesis Cascade
There are five steps in the thyroid synthesis process. First the precursor protein thyroglobulin (TG) is made from thyrocytes in the thyroid follicular cells; this precursor protein does not yet contain iodine. Step #2 iodide is brought from the circulation to the thyrocytes and into the follicular cells. Step 3: the enzyme thyroid peroxidase (TPO) is activated and exacts three roles: oxidation, organification, and coupling reaction to ultimately form the four-iodine atom containing Thyroxine (T4). T4 is the major thyroid hormone product of the thyroid synthesis circulating in the bloodstream. T4 the inactive form of thyroid hormone is converted to the active form of thyroid hormone triiodothyronine (T3), comprised of 3 iodine atoms.

The thyroid produces 90% inactive T4 thyroid hormone and 10% active thyroid hormone T3. Thyroid hormone is stored bound to thyroglobulin in the follicular stores. Upon TSH stimulation proteolytic enzymes cleave thyroglobulin and T4 and T3 are released into the bloodstream. Thyroid hormones are lipophilic and are transported in the blood via transport proteins. Both circulating thyroid hormones (T4 and T3) exert direct negative feedback on TRH synthesis in the hypothalamus. Peripheral deiodination of T4 to T3 in the liver and kidney accounts for approximately the other 80-90% of circulating T3.

There are three types of deiodinase enzymes, type I (DIO1), II (DIO2), and III(DIO3).
DIO1 primarily functions in the liver, kidney, and thyroid. DIO2 predominates in the brown adipose tissue, skeletal muscle, heart, and CNS. DIO3 is primarily located in the CNS, skin, and placenta. The majority of T4 to T3 conversion is through catalyzation by deiodinase type 2 which is found in many tissues throughout the body. DIO1 also converts T4 to active T3. DIO3 is DEACTIVATING meaning it converts T4 into reverse triiod
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7 min

About Endocrinology Review

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This Endocrine Review Course is hosted by Dr. Saif Borgan (Cleveland Clinic trained board certified endocrinologist in the United States) and Dr Kristen Lee (Endocrine Fellow at Northwestern…