Mental Health Effects of Endocrine Dysfunction: Symptoms, Assessment and Treatment Strategies

David Reinhardt, Ph.D., ABMP www.CenterforHealthScience.com “One Half Of What You Were Taught As Medical Students Will In 10 Years Have Been Shown To Be Wrong, And The Trouble Is, Your Teachers Don’t Know Which Half.

SIDNEY BURWELL (1893-1967) BMJ 2, 113, 1956 Psychologists

When we see a patient with sadness, fatigue, anhedonia, weight gain and decreased sex drive we look for psychological factors causing this change. Perhaps trauma, maladaptive thought processes, self-esteem issues, grief, loss and other problems in thinking. Psychiatrists

Most psychiatrists would see this as Depressive Disorder, a disease like all medical diseases, with chemicals to control symptoms and to hopefully cure. Medicine can help with hypertension, and bacterial infections, and broken bones after all, why not depression? Traditional View of the Endocrine System

Traditionally, the endocrine system was thought as consisting of 10 organs:

Pineal gland Adrenal glands Pituitary Sex organs- Parathyroids and testes and Their Sources

• • •Epinephrine • •Noradrenline •Estriol •Androstendione •Estrone Hormones and Their Sources Blood

•Leukotrienes •Thromboxane Hormones and Their Sources Bone

• Hormones and Their Sources Brain/CNS

•Cortistatin •-like peptide1 • • • •Serotonin Hormones and Their Sources Breasts

•Prolactin • Hormones and Their Sources

• •Gastric inhibitory polypeptide • • Hormones and Their Sources Endothelium

• •Asprosin •Prostacyclin • •Fat cells •Estrone • •Prolactin Hormones and Their Sources

•Atriopeptin •Brain natriuretic Hormones and Their Sources Hypothalamus •Anti-diuretic •Corticotropin-releasing hormone •Gonadotrophin-releasing hormone •-releasing hormone • Hormones and Their Sources Hypothalamus

•Melanocyte-stimulating hormone • • Hormones and Their Sources Hypothalamus

•Prolactin releasing hormone • •Thyrotropin-releasing hormone •Vasoactive intestinal peptide Hormones and Their Sources

•Enkephalin • • •Uroguanylin • •Dehydroepiandrosterone •Thrombopoietin Hormones and Their Sources

•Angiotensinogen • •Angiotensin •Thrombopoietin •Hepcidin •Triiodothyronine Hormones and Their Sources Muscle tissue

•Irisin •Thrombopoietin Hormones and Their Sources Ovaries • Human chorionic gonadotrophin • •Dehydroepiandrosterone •Dihydrotestosterone Hormones and Their Sources Ovaries

• • •Estrone •Relaxin •Inhibin • Hormones and Their Sources Pancreas

• • •Ghrelin • •Glucagon •Vasoactive intestinal- •Glucagon-like peptide peptide Hormones and Their Sources Parathyroid Glands •

Pineal Gland • Hormones and Their Sources Pituitary Gland

•Adrenocorticotropic hormone •Follicle stimulating hormone •Melanocyte-stimulating hormone Hormones and Their Sources Pituitary Gland

•Prolactin • •TSH • • •Growth hormone •Oxytocin Hormones and Their Sources Prostate

•Dihydrotestosterone Hormones and Their Sources Skin •Prolactin •Calcidiol • •Dihydrotestosterone •Melanocyte-stimulating hormone Hormones and Their Sources Small intestine

•Galanin •Guanylin •Gastrin • •Ghrelin •Serotonin •Glucagon-like peptide •Pancreatic peptide YY Hormones and Their Sources Small Intestine

•Serotonin • Somatostatin •Vasoactive intestinal peptide •-dependent insulinotropic peptide Hormones and Their Sources

Stomach

•Gastrin •Ghrelin Hormones and Their Sources Testes

•Inhibin •Anti-Müllerian hormone •Estradiol •Dehydroepiandrosterone •Testosterone •Dihydrotestosterone •Androstenedione Hormones and Their Sources Thyroid

• •Thyroxine •Triiodothyronine Hormones and Their Sources Uterus • Prolactin Multiple Organs • Pituitary adenylate cyclase-activating peptide • • Somatostatin Cochrane Library

• Cochrane is the single most respected research organization worldwide due to its uniform and strict standards of analysis • Cochrane is a global independent network of over 13,000 researchers and health professionals • The group conducts systematic reviews of health-care interventions and diagnostic tests and publishes them in the Cochrane Library The group is non-profit and does not accept commercial funding, work is funded by national and international governments and NGOs, private foundations and individuals

Cochrane studies are available for free in nearly every country in the world, but in the us access is restricted as a paid product of Wiley and Sons. abstracts can be reviewed for free at: https://www.cochranelibrary.com/cdsr/reviews Importance of Thyroid Evaluation

• One woman in eight will be diagnosed with thyroid disorder during her lifetime. • Up to 60 percent of those with thyroid dysfunction are unaware of their condition. • Thyroid disorders occur in women at up to 20 times the male rate Thyroid disorders occur in women at up to 20 times the male rate

38% of women between 45 and 64 years old are diagnosed with a thyroid disorder

One study in Colorado found that an additional 20% of this population have subclinical thyroid dysfunction.

(American Thyroid Association: https://www.thyroid.org) Common Hypothyroid Symptoms

• Depression • Sensitivity to cold • Fatigue • Irregular menstruation • Impaired memory • Muscle aches, stiffness • Thinning hair • Constipation • Weight gain Common Hypothyroid Symptoms cont. • Dry skin • Pain, swelling in joints • Puffy face • Slowed heart rate • Hoarseness • Enlarged thyroid gland • Muscle weakness • Elevated cholesterol (Mayo Clinic) Common Hyperthyroid Symptoms

• Anxiety and irritability • Fine, brittle hair • Difficulty sleeping • Weight loss • Fatigue, weakness • Rapid heartbeat • Skin thinning • Irregular heartbeat Common Hyperthyroid Symptoms cont.

• Sensitivity to heat • Sweating • Pounding heart • Changes in menstration • Increased appetite • Changes in bowel patterns • Tremor • An enlarged thyroid gland

(Mayo Clinic) SCIENCE-Y STUFF The thyroid hormone process starts with Thyroglobulin, a protein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. The enzyme Thyroperoxidase triggers residues in the thyroglobulin to bond with and form 2 intermediates, which then combine in different ratios to form thyroxine, called T4, and triiodothyronine, which is T3. Regulation of hormone release begins in the hypothalamus. the hypothalamus releases thyrotropin-releasing hormone (TRH) in response to signal molecules from organs throughout the body.

Current knowledge indicates it is inhibited by serotonin, and probably GABA, somatostatin, and corticotropin-releasing factor. appears to increase release of both TRH and somatostatin. glycine deficiency may inhibit gaba release which may in turn increase TRH. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release. TRH travels to the pituitary gland. in response, the pituitary gland then releases thyroid-stimulating hormone (TSH) into the blood. TSH is released in proportion to TRH levels and as part of a feedback loop in response to low T3.

Increased TSH triggers the thyroid to produce more T4 and later, T3.

Much of the conversion of T4 to T3 occurs primarily in the liver, and about 20% in the thyroid itself. Some of the T4 is converted to reverse triiodothyronine (RT3), an inactive form of T3, by removal of an iodine atom by the enzyme (D2).

Deiodinase also breaks down some of the T4 to become diiodothyronine (T2).

Reverse T3 is a seldom considered thyroid hormone that seems to play a role in the body’s response to T3. Reverse T3 is a seldom considered thyroid hormone that seems to play a role in the body’s response to T3.

Few studies have looked at the causes and effects of elevated RT3.

Many naturopaths and other "alternative" specialists suspect the balance between T3 and reverse T3 is a driving force for many of the symptoms labeled as "depression" that are seen with hypothyroidism. We do know that the body produces more reverse t3 in times of severe illness or starvation, possibly to preserve energy.

Some experts suspect reverse t3 is a balancing force that we come up against that interferes with losing weight during dieting.

When humans (and animals) get sick, we see common symptoms are fatigue, body aches, an “off” mood and loss of interest. reverse t3 could be a major but misunderstood player. BASIC THYROID PANEL

TSH (thyroid-stimulating hormone) Total T4 (thyroxine) Free T4 (thyroxine) and Free T3 (triiodothyronine) If not covered by insurance, costs about $75 Additional Tests rT3 (Reverse T3) FTI (Free Thyroxine Index) T3U (Resin T3 Uptake) Thyroid Other Tests

A physical examination of the thyroid is standard when thyroid symptoms are present. It is not uncommon for the first symptom to be a patient describing a tightness or lump in the throat, which you may be tempted to attribute to anxiety. Other Tests cont.

A thyroid ultrasound may be ordered to examine the thyroid for cysts, nodules or tumors.

Nodules can cause too little or too much thyroid hormone to be produced. Basal Body Temperature is an old concept, and one which is still debated. Most allopaths don’t believe in this. Lab Results Normal Ranges

TSH 0.45-4.5 uU/ml (>10 years) (TT4) Total T4 4.5-12.0 ug/dl (FT4) Free T4 0.82-1.77 ng/dl (>19 years) (FT3) Free T3 230-619 pg/d (T3U) Resin T3 Index 24-39 (>18 years) (FTI) Free Thyroxine 4-11 Thyroid Antibodies Negative (LabCorp) Factors That Affect Thyroid Test Results

-Biotin supplements (vitamin B7), often taken to improve the hair give false results -B vitamins should be discontinued at least 3 days before labs Factors, cont.

• Stress • Pregnancy • Sleep deprivation • Stage of menstrual cycle • Iodine • Fasting/non-fasting • Illness variation Factors, cont.

• Lithium • Most anticonvulsants • NSAIDS • Immunomodulating drugs • Lasix • Chemotherapeutic drugs • Heparin • Steroids Available Treatments Synthroid (T4) Absorption inhibited by coffee Cytomel (T3) Absorption may be inhibited by antacids May interact with some antidepressants Desiccated Thyroid (Armour, others) Absorption may be inhibited by coffee Not appropriate if elevated thyroid antibodies Common Thyroid Lab Patterns- Primary Hypothyroidism

TSH = Elevated Total T4 = Normal or low Free T4 = Normal or low Free T3 = Normal or low rT3 = Normal FTI = Normal or low T3U = Normal or low Antibodies = Negative or Positive Consider T4,T3, Armour Primary Hyperthyroidism

TSH = Low Total T4 = Normal or elevated Free T4 = Normal or elevated Free T3 = Normal or elevated rT3 = Normal FTI = Normal T3U = Normal Antibodies = Positive Consider anti-thyroid treatments Hypothyroidism Secondary to Pituitary Hypofunction

TSH = Normal or low Total T4 = Normal or low Free T4 = Normal or low Free T3 = Normal or low rT3 = Normal FTI = Normal T3U = Normal Antibodies = Negative Consider adrenal function tests Thyroid Underconversion

TSH = Normal Total T4 = Normal or elevated Free T4 = Normal or elevated Free T3 = Low rT3 = Low FTI = Normal or elevated T3U = Low Antibodies = Negative Consider T3 supplementation; Consider Diurinal Cortisol Test Thyroid Overconversion

TSH = Normal Total T4 = Normal or low Free T4 = Normal or low Free T3 = Elevated rT3 = Normal FTI = Normal or low T3U = Elevated Antibodies = Negative Consider or PCOS Thyroid Binding Hormone Elevation

TSH = Normal Total T4 = Normal Free T4 = Low Free T3 = Low rT3 = Normal FTI = Normal or low T3U = Low Antibodies = Negative Consider exogenous exposure Thyroid Resistance TSH = Normal Total T4 = Normal Free T4 = Normal Free T3 = Normal rT3 = Normal FTI = Normal T3U = Normal Antibodies = Negative "All normal" with symptoms- Consider adrenal tests Nutritional management of thyroid disorders

• Vitamin A • Zinc • Vitamin D • Iodine with caution • Selenium, with caution • Not Tyrosine Herbs and Other Nutrients

• Ashwagandha (Withania • Kelp, seaweed Somnifera) • Bugleweed • Gugulu (Commiphora • Antioxidants Muku) • Omega-3 fatty Acids • Eleuthero (Siberian • B Complex Ginseng) Bipolar Illness—What do we know?

• We know that mania and hypomania can be triggered by antidepressants • We know that antipsychotics, being major tranquilizers, can reduce active mania, and we also know that despite hype, antipsychotics have no scientific validity for maintenance Bipolar Illness-cont.

We also know that the full range of psychotropics are used for bipolar 1 and 2, but lithium treatment is the most effective to reduce cycling, although limited studies find usefulness for valproic acid (Cochrane Reviews) Mood Stabilizers and Risk of Stroke in Bipolar Disorder

• Mood stabilizers as a group are significantly associated with the increased risk of stroke in patients with bipolar disorder. • Among individual mood stabilizers, acute exposure to had the highest risk of stroke, particularly the ischaemic type. Mood Stabilizers cont.

• Acute exposure to valproic acid elevated the risk of hemorrhagic stroke. • In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke. The British Journal of Psychiatry, 1–6. doi:10.1192/bjp.2018.203 A New Treatment for Bipolar Depression

“ Imagine a new treatment for bipolar depression that: Has not caused medical problems in over 20 years of research Does not cause weight gain or diabetes Has no adverse effects for most people (and if they occur, are short-lived with dose reduction), including no daytime sedation or fatigue, even during titration What treatment am I talking about? Good old thyroid hormone”

Psychiatric Times, Part 1. James Phelps, M.D. Updated September 7, 2018 Dr. Phelps recommends the following protocol for Bipolar Disorder

1. Consider as an augmentation in depressed patients with a TSH level greater than 2.5 mU/L, especially in bipolar depression (a nifty alternative to adding an antidepressant, with its attendant risks of inducing cycling and mixed states; or to buy time while slowly tapering an antidepressant). 2. Start with high initial doses, such as 50ug (one half pill daily for a week then one daily”), at least for patients with significant depression. Target a TSH level at least down to median for age: 1.5 mU/L to age 50; 1.6 mU/L to age 60; 1.7 mU/L to age 70; and 1.8 mU/L to age 80.

Any level of TSH between 1.0 mU/L and median is easily justified per the available literature. If there is no clearly associated risk, why not get there? Just as we “push” medications to the top of their dosage range (if fully tolerated yet not fully effective), we should suggest levothyroxine to a TSH around 1.0 mU/L to call its trial adequate. Nutrients For Bipolar Illness

• Omega 3 fatty acids • N-acetylcysteine. • Choline • S-adenosylmethionine • Inositol (SAMe) • 5-hydroxy-L-tryptophan • Lithium Adrenal Insufficiency

• Moderate to severe adrenal insufficiency can be caused by a disease of the adrenal glands such as fungal infections, cancer, tuberculosis or by physical injury. • Adrenal insufficiency commonly co-occurs with autoimmune disorders. Adrenal Insufficiency cont.

• Primary adrenal insufficiency is called Addison’s disease. Labs will show abnormally low cortisol and often low aldosterone. • Addison's disease symptoms usually develop slowly, often over several months. Often, the disease progresses so slowly that symptoms are ignored. Symptoms of Addison’s Disease

• Depression • Salt craving • Behavioral symptoms • Low blood sugar • Irritability • Nausea, diarrhea • Extreme fatigue • Abdominal pain • Weight loss • Muscle or joint pains • Darkening of the skin • Body hair loss • Low blood pressure • Sexual dysfunction in women Cortisol

• Cortisol controls the sleep/wake cycle. It is released during times of stress to give an energy boost to handle emergency situations, the flight or fight response • It helps control the body’s use of fats, proteins and carbohydrates; suppresses inflammation; regulates blood pressure; increases blood sugar; and can also decrease bone formation. Cortisol Science

• As with the thyroid system, the release of cortisol is initiated in the hypothalamus which produces corticotropin-releasing hormone (CRH). • This hormone stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH). • ACTH then stimulates the adrenal glands to make and release cortisol hormones into the blood. Tests For Adrenal Issues

• Test • Sodium • -Cortisol • Adrenal antibodies • ACTH • ACTH stimulation test- • Potassium • Diurinal cortisol test (saliva, 4 sample Adrenal Burnout, Adrenal Fatigue

• Adrenal fatigue is a term applied to a collection of nonspecific symptoms, such as nervousness, sleep disturbances. body aches, fatigue, and digestive problems. • This term is frequently used by naturopaths and other alternative professionals, but it is not accepted as a diagnosis by Western allopathic medicine. Adrenal Burnout, Adrenal Fatigue cont.

Before dismissing adrenal fatigue, it may be important to remember that until a few years ago the diagnosis of Fibromyalgia was dismissed, and many doctors still reject Chronic Fatigue Syndrome. Diurinal Cortisol Indicators

• Cortisol production is normally at its highest 30 minutes after waking and declines steadily during the day, reaching its lowest point at bedtime. Those with adrenal gland dysfunction generally have irregularities in their diurnal cortisol curves. • Overall higher than normal cortisol production throughout the day can result from prolonged stress demands. General symptoms include feeling “tired but wired,” food cravings, insomnia and anxiety. Diurinal Cortisol Indicators cont.

• Chronic fatigue shows an elevated morning cortisol with levels dropping off rapidly during the day. General symptoms include mid-day energy drop, drowsiness and poor exercise recovery. • The burnout pattern, also commonly called “adrenal fatigue” is really a reflection of low overall cortisol during the day. General symptoms include day-long fatigue, irritability, food cravings, insomnia and exhaustion. Chemistry Panel Markers Of Adrenal Disorders The CMP (Comprehensive Metabolic Panel) can provide clues to when more advanced lab testing is needed. This is not diagnostic!

Adrenal Hypofunction Adrenal Hyperfunction • Potassium = Increased • Potassium = Decreased • Sodium = Decreased • Sodium = Increased • Chlorides – Decreased • Chlorides = Increased • Glucose = Decreased • Glucose Increased (>100) (<85) • Triglycerides = Increased Herbal Adjuncts Of Adrenal Disorders

• Ashwagandha • Panax Ginseng • Boerhavia diffusa • Rhodiola • Holy Basil Leaf Extract • Eleuthero Health care is a team sport. Don’t hesitate to present your ideas, and don’t hesitate to suggest labs and treatment strategies with your team members!

Some final questions…

As psychologists, should we be requesting thyroid labs on our depressed and anxious patients?

Should we be counseling on nutrition, a topic that the AMA has recently called missing from medical training?