[Pubmed] Fatigue syndrome due to endocrine diseases


first. SUMMARY

Overview of Endocrine Fatigue Syndrome (EFS) describes the different clinical manifestations of fatigue in endocrine disease. This review lists various endocrine and non-endocrine causes of fatigue in endocrine disease and shares practical clinical tips to help with the differential diagnosis.


Fatigue has been defined as physical and/or mental exhaustion that can be caused by stress, mental and physical illness, medication. first Fatigue is a term used to assess the extent to which the average person quickly becomes exhausted. Fatigue refers to the presence of physical and/or mental exhaustion at a level of work or stress that would not normally cause such burnout. 2 Fatigue, or getting tired easily, is the second most common symptom in the family clinic, and one of the most common causes of fatigue is endocrine disease. 3

Fatigue can be a manifestation of endocrine abnormalities, which can include disorders of the thyroid gland, diabetes, pituitary gland, and gonads, abnormalities of bone and mineral metabolism such as vitamin D deficiency and hyperparathyroidism. Fatigue can also be one of the symptoms that patients often complain about these disorders. On the other hand, fatigue may persist after achieving hormonal equilibrium with appropriate endocrine therapy. Both scenarios can be referred to as endocrine fatigue syndrome (EFS).


Endocrine fatigue syndrome (EFS) can be defined as a multifactorial syndrome that causes fatigue or fatigue, occurring in individuals with endocrine disease. It may be one of the manifestations of the disease or may arise during treatment, EPS may be part of the natural progression of the disease, may be due to complications or comorbidities, or may be due to erosion factors.


Although the terms “fatigue” and “depression” have been used synonymously, they are not the same thing and have slight differences. 4 One must be careful in ruling out depression before diagnosing EFS. The causes of fatigue were listed earlier with simple mnemonic “LEMON”: Lifestyle, Endocrinopathies, Metabolic derangements, Observer error, or Nutritional deficiency – Lifestyle, Endocrine diseases, Metabolic changes, Control error or Undernutrition. 5

Fatigue impairs physical as well as mental performance, and reduces quality of life. Therefore, when a patient complains to a doctor about fatigue, these patients should be medically examined and focused on endocrine system disease. This review lists common causes of EFS including endocrine and other causes that remain after treating or ruling out endocrine disorders. We described general neuropsychiatric and musculoskeletal symptoms and signs and general symptoms that aid in the differential diagnosis of EFS (Table 1.2). and clinical pearl to help diagnose and manage EFS. Some of the most common endocrine fatigue syndromes are diabetic fatigue syndrome (DFS) and thyroid disorder fatigue.

Table 1: Fatigue syndrome due to endocrine diseases
Table 2: Causes of fatigue in endocrine diseases

a. Diabetic Fatigue Syndrome (DFS)

The pre-defined diabetic fatigue syndrome. 4Fatigue can be a symptom of diabetes and it can persist even after stable glycemic control is achieved. The most common cause of DFS is uncontrolled blood sugar and is manifested by hyperglycemia, episodes of hypoglycemia, or high blood sugar fluctuations. Current diabetes management is often goal-oriented rather than patient-oriented. This leads to patient dissatisfaction despite good blood glucose status. This may be related to glycaemic unhappiness and symptoms of fatigue complications including microvascular and macrovascular disease, as well as heart failure that can lead to DFS. One of the causes of fatigue in patients with diabetes is associated endocrine diseases such as hypothyroidism, Cushing’s syndrome, hypogonadism or Addison’s disease. Related medical conditions such as anemia, vitamin deficiency, and electrolyte disturbances or use of certain medications such as diuretics, statins, or beta blocks may be associated with DFS. 4

b. Fatigue in thyroid disorders

The most common symptoms of hypothyroidism are fatigue and depression. 6 These symptoms were reversible with levothyroxine therapy and stabilized serum TSH levels. Approximately 7%-10% of patients whose TSH levels are normalized with LT4 monotherapy may have persistent symptoms of fatigue. 7 FT3 values ​​below the lower limit of normal are observed in approximately 15% of hypothyroid patients receiving L-T4 monotherapy. 8 It has been suggested that tissue hypothyroidism may persist in such patients even when serum TSH has been normalized. 9 Several studies have shown improvements in fatigue scores and other symptoms of hypothyroidism with a combination of T3 and T4 therapy. ten However, larger trials are needed to determine the role of combination therapy in controlling hypothyroidism. Newer tank constructions have begun to take this into account. 11


a. Screening

People with fatigue should be clinically examined for endocrine disease by taking medical history and performing physical examination

Individuals with fatigue and neuropsychiatric and/or musculoskeletal symptoms should be evaluated for EFS, including disorders of bone mineral metabolism, thyroid function, and diabetes.

b. Diagnose

Individuals with a suggestive history or physical examination should be evaluated for specific endocrine disorders, to rule out EFS.

EFS-related laboratory tests must be indicated based on an index of economic considerations and clinical suspicion.

c. Evaluate

Non-medical and non-endocrine factors must be evaluated and addressed, along with endocrine management, in EFS.

Patients with “well-controlled” endocrine disease who often complain of fatigue should be evaluated for other endocrine diseases and their complications.

The concomitant combination of medication use and lifestyle habits must be considered as a potential cause of EFS.

d. Treatment

A trial of vitamin D and calcium therapy could be considered in South Asians with fatigue, considering the prevalence of vitamin D deficiency.

Hormone replacement or supplementation should be initiated as a treatment for EFS, with no documented endocrine deficiency or impairment.

People with EFS must be regularly monitored during treatment.

e. Clinical pearls

– Rule out deficiencies in macronutrients, micronutrients, electrolytes, sleep, and exercise before further evaluation.

Exclude psychological causes of fatigue along with biochemical evaluation.

Sudden onset of fatigue in patients with well-controlled diabetes, pale skin, and reduced need for antidiabetic agents suggest screening for renal disease and hypothyroidism.

Fatigue, dyspnea and reduced exercise capacity in diabetic patients suggest testing for heart failure

Fatigue with muscle symptoms suggestive of vitamin D osteocalcin deficiency and Cushing’s syndrome

Fatigue with neuropathic symptoms mainly suggests diabetic neuropathy, hypothyroidism, and hypoparathyroidism.

Fatigue with tetany suggests hypoparathyroidism

Cyclic fatigue indicating electrolyte disturbances or premenstrual syndrome (PMS)

Fatigue with skeletal symptoms mainly indicates hyperparathyroidism or osteoporosis.

Fatigue with loss of libido or other sexual dysfunction indicative of hypogonadism, including menopause (women) or menopause (men)


EFS is an important cause of systemic fatigue. Through this review, we hope to highlight the clinical pathway in the diagnosis and management of this important but common problem associated with various endocrine diseases.


1. Fatigue. http://www.dictionary.com/browse/ fatigues=t. Accessed 10 May 2018.

2. Jain A, Sharma R, Choudhary PK, Yadav N, Jain G, Maanju M. Study of fatigue, depression, and associated factors in type 2 diabetes mellitus in industrial workers. Ind Psychiatry J. 2015;24:179.

3. Gregory Kaltsas G, Vgontzas A, Chrousos G. Fatigue, Endocrinopathies, and Metabolic Disorders. PM R. 2010;2:393-8.

4. Kalra S, Sahay R. Diabetes Fatigue Syndrome. Diabetes Ther 2018; 9:1421–1429.

5. Kalra S, Sahay. R.A LEMON a Day Keeps Fatigue Away-The ABCDE of Fatigue. Euro. Endocrinol. 2018;14:15-16

6. Kalra S, Balhara YPS. Euthyroid Depression: The Role of Thyroid Hormone. Recent Pat Endocr Metab Immune Drug Discov. 2014; 8:38-41.

7. Panicker V, Evans J, Bjoro T, Asvold BO, Dayan CM, Bjerkeset O. A paradoxical difference in relationship between anxiety, depression and thyroid function in subjects on and not on T4: findings from the HUNT study. Clin. Endocrinol 2009; 71: 574–580.

8. Escobar-Morreale HF, Del Rey FE, Obregón MJ, de Escobar GM. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology. 1996;137:2490-502.

9. Kalra S, Khandelwal SK. Why are our hypothyroid patients unhappy? Is tissue hypothyroidism the answer? Indian J Endocrinol Metab;. 2011;15(Suppl2): S95-98.

10. McAninch EA, Bianco AC. The swinging pendulum in treatment for hypothyroidism: from (and towards?) combination therapy. Front. Endocrinol. 2019; 10:446.

11. Kalra, Unnikrishnan AG, Kalhan A. Redefining euthyroidism: A biopsy for social construct. Thyroid Res Pract 2020; 17:2-3.

Source: https://pubmed.ncbi.nlm.nih.gov/33819252/

The article is translated and edited by ykhoa.org – please do not reup without permission!

Translator: ToanTran.

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