Unilateral gynecomastia as an initial presentation of hyperthyroid Graves’ disease

Summary Graves’ disease is an autoimmune condition leading to the activation of and an increase in thyroid hormone secretion. Manifestations of hyperthyroidism in Graves’ disease can vary among people. In this case, we report a 24-year-old Thai man with a rare presentation of unilateral gynecomastia along with symptoms of thyrotoxicosis. Physical examination revealed a 3 cm non-tender palpable glandular tissue beneath and around the left areola without nipple discharge and moderately diffuse thyroid enlargement with thyroid bruit. Thyroid function test showed a typical thyrotoxicosis state with elevated serum-free T4 and decreased serum TSH. His diagnosis of Graves’ disease was confirmed biochemically with a highly elevated anti-TSH receptor antibody. Early treatment with anti-thyroid medication was given first, followed by Radioiodine treatment (RAI) for definitive treatment due to high level of anti-TSH receptor antibody, enlarged thyroid and severe thyrotoxicosis presentation at a young age, which might not resolve by anti-thyroid medication alone. The patient responded well to treatment and achieved complete resolution of unilateral gynecomastia with clinically and biochemically euthyroid within 3 months after treatment. No recurrent gynecomastia was found during the 2-year follow-up. Learning points Characteristic of gynecomastia in hyperthyroidism is usually presented with bilateral progressive gynecomastia; however, unilateral gynecomastia is occasionally found as a presentation of hyperthyroidism. Complete resolution of gynecomastia without recurrence can be achieved within a few months of treatment after thyrotoxicosis is resolved in patients with hyperthyroidism with the recent development of gynecomastia. RAI for definitive treatment is recommended in young adult patients expressing very high anti-TSH antibody level with severe thyrotoxicosis.

Myxoedema ascites-Rare presentation of long standing hashimotos thyroiditis

Hypothyroidism is among the common clinical conditions which are encountered in the medicine OPD. An autoimmune disorder called Hashimoto’s thyroiditis is a common cause for hypothyroidism followed by over response to hyperthyroidism treatment, radiation therapy, medications, congenital disease etc. Patients can present with sensitivity to cold, weight gain, constipation, menstrual abnormalities, and slow mentation with irritability, dry skin, hair loss, and fatigue. Rarely, uncontrolled hypothyroidism can present as pericardial effusion, pleural effusion and ascites. Ascites as the feature of hypothyroidism is uncommon and only less than four percent of patients with hypothyroidism /develop ascites.As it is rarely presented as ascites so its diagnosis is delayed but once it is diagnosed, treatment leads to clinical improvement.: A 20-year-old female presented to medicine OPD with non- tender abdominal distension, vomiting. She was a known case of Hashimoto's thyroiditis an autoimmune disorder; however, she was not compliant to thyroid medication. All necessary investigations were carried out to rule out the cause for ascites. With all the negative reports including imaging and supportive fluid cytology we attributed the symptoms to uncontrolled hypothyroidism as the patient was non-compliant to the thyroid medications. Also the picture of macrocytic anaemia in our patient supported the diagnosis. She was started on levothyroxine and was counselled. On a follow-up visit there was dramatic improvement of all the symptoms including ascites and her TSH was normal-2.017. Ascites as a symptom of hypothyroidism is rare and its pathophysiology is not fully understood however there are few theories and studies in the past which do explain ascites as the manifestation of hypothyroidism. Severe uncontrolled hypothyroidism though uncommon but can cause ascites. Being a reversible cause of ascites, it becomes important for clinicians to take hypothyroidism as one of the differential diagnosis for ascites. Our case supports the need of taking hypothyroidism as one of the cause, as it is easily treatable and patient can show dramatic improvement.

UNEXPLAINED DELIRIUM : THINK OF THYROID STORM

Background: Thyroid storm is a life-threatening Endocrine emergency with an incidence rate of 1% to 2% all over the world. It is a systemic condition leading to increased production of Thyroid Hormone and its release leading to Thermoregulatory, Adrenergic, Neuropsychiatric, Cardiovascular, and Abdominal Manifestations. Thyroid storm with Malignant Arrhythmia and delirium both together is rare entity, but the mortality rate is very high. The presentation of Malignant Arrhythmias and delirium together in the initial phase of the disease is much less common with only a few isolated cases described in the scientic literature. Objective: To present a case in which a patient had two simultaneous complication of thyroid storm i.e. delirium and ventricular tachycardia. Case Study: We report a 65 years-year-old man who came with complaints of Diarrhea, Fever, Breathlessness and psychosis. His serum tsh was <0.015 and anti tpo antibodies was 83. He was diagnosed to be in Thyroid storm and later had complications including Ventricular Tachycardia and delirium in an undiagnosed case of Hyperthyroidism. He was started on anti thyroid medication and slowly as his condition improved he was discharged. Conclusion: Patients with Thyrotoxicosis need to be closely monitored for complications since its early diagnosis and treatment may save lives.

Hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism: an uncommon cause of acute muscle paralysis

Hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism is an uncommon clinical phenomenon characterised by lower limb paralysis secondary to hypokalaemia in the background of subclinical hyperthyroidism. In this article, we report a patient who presented with progressive lower limb muscle weakness secondary to hypokalaemia that was refractory to potassium replacement therapy. He has no diarrhoea, no reduced appetite and was not taking any medication that can cause potassium wasting. Although he was clinically euthyroid, his thyroid function test revealed subclinical hyperthyroidism. His 24-hour urine potassium level was normal, which makes a rapid transcellular shift of potassium secondary to subclinical hyperthyroidism as the possible cause. He was successfully treated with potassium supplements, non-selective beta-blockers and anti-thyroid medication. This case report aimed to share an uncommon case of hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism, which to our knowledge, only a few has been reported in the literature.

Impact of Thyroid Disease on Bone Mineral Density Preservation in Patients With Osteoporosis and Idiopathic Hypercalciuria

Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures. It is not known if thyroid disease impacts the degree of urine and bone mineral abnormalities in patients with IHC and osteoporosis (OPO). Methods: Retrospective chart review from a private endocrinology clinic identified 62 consecutive patients with OPO (fragility fracture and/or t-score ≤-2.5 on bone density scan) and concomitant diagnosis of IHC (urine calcium &gt; 4.0 mg/kg weight/d when intaking low-moderate calcium amounts). Patients were classified into two groups: those with thyroid disease (Thy+, if presence of autoimmune thyroid disease [AITD] with high antibody titers and/or long-term thyroid medication use) and those without (Thy-). Comparisons were made between the two groups for severity of renal disease (urine calcium) and bone disease (number of fragility fractures, and BMD response to therapy). Results: Of 55 women and 7 men identified with both OPO and IHC, 30 were Thy+ (4 with Graves’, 11 with confirmed Hashimoto’s, 13 taking levothyroxine for presumed Hashimoto’s and 2 with thyroid cancer), and 32 were Thy- (including 2 with type 1 DM, 1 with vitiligo, and 6 with non-toxic nodular goiters requiring biopsies). Thy+ were compared to Thy- with respect to: mean age (70.7 ± 7.3 vs. 70.8 ± 9.3 y), sex (97% vs. 81% women), 24-hr urine calcium at diagnosis (317 ± 75 vs. 311 ± 68 mg), presence of fragility fracture (50% vs. 59%), use of thiazide (83% vs. 78%), and use of anti-fracture pharmacotherapy (73% vs. 84%). 50 patients had adequate comparative longitudinal BMD data. A (+) BMD response was based on consistent increases in BMD and/or t-scores across all spine and hip sites, and a (-) BMD response was classified by decreased BMD and/or t-scores across all sites. For Thy+ vs. Thy- patients, there were 25% vs. 69% (+) BMD response, 38% vs. 12% (-) BMD response, 21% vs. 4% with no significant BMD response, and 17% vs. 15% with mixed BMD responses. Conclusions: In this group at high risk for future fragility fractures, much lower rates of BMD preservation was seen in the Thy+ as compared to the Thy- patients. Overall, AITD and medical thyroid disease was very common (48%) in this cohort of patients with IHC and OP. However, this high rate may be confounded by the selective nature of the specialty clinic population. Further research needs to delineate the impact of AITD and thyroid medication use on the progression and treatment of patients with IHC and OPO.

Reverse T3 in Patients With Hypothyroidism, Helpful or a Waste of Time?

Background: Reverse T3 (rT3) is a biologically inactive form of T3 that is created by peripheral 5 deiodination of T4 by type 1 and type 3 deiodinases and may block T3 binding to the thyroid hormone receptor. As about 15% of patients on L-T4 replacement with a normalized TSH report continued fatigue and other hypothyroid symptoms, efforts are needed to understand why this occurs and how it can be corrected. Decades ago, endocrinologists realized that in severe illnesses, rT3 is often high and T3 is often low and termed this “sick euthyroid syndrome”. However, more recently, alternative doctors, including functional medicine doctors, have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor. Without peer-reviewed publications, these functional medicine doctors rely heavily on rT3 levels to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe them L-T3-only preparations to try to lower the rT3. Also poorly characterized in the literature are the effects of hypercortisolism and hypopituitarism, both of which should modulate the expression of deiodinases to increase rT3. Hypotheses: 1) Patient rT3 levels will vary significantly with the type of thyroid medication taken. 2) Patient rT3 levels will be clinically significant in the management of patients on thyroid medications. 3) Hypercortisolism and hypopituitarism will increase rT3 levels. Methods: The most recent rT3 measurements were analyzed from 621 patients currently being managed by TCF. The upper limit of normal for rT3 at either Quest or LabCorp, which is usually 24.1 ng/dL was used as a cut-off for a high result and below 9.2 ng/dL as the low cut-off. Results: Elevate rT3 levels was seen in 3% of patients of patients not on thyroid replacement (5/143), seen in 8% of patients (17/203) taking desiccated thyroid. It was more prevalent in patients taking desiccated thyroid with synthetic T3 (27%, 7/26) or T4 (15%, 16/104) and was seen in 15% of patients (9/58) taking synthetic T4 alone. Changes were made to the amount or type of medications in 199 patients. Levels of rT3 levels were outside the normal range in 27% of these patients (54/199), being above normal range in 16% of these patients (32/199). Hypercortisolism was seen in 37 patients, 36 from Cushing’s disease, however above normal rT3 was seen in only 2 patients. Hypopituitarism was diagnosed in 22 patients, only one had above normal rT3 levels because they couldn’t afford their growth hormone replacement. Conclusion: Measuring rT3 may be helpful in patients who are already on thyroid treatments, and is of greater importance in patients taking synthetic preparations. It is not recommended in patients who are not taking thyroid medicine (even if experiencing hypercortisolism) or in patients with hypopituitarism that are taking adequate hormone replacement.

Two Cases of Graves’ Hyperthyroidism Treated With Homeopathic Remedies Containing Herbal Extracts from Lycopus spp. and Melissa officinalis

Background: Plant extracts from species of Lycopus (bugleweed) and Melissa officinalis (lemon balm) have long been used as folk remedies in the treatment of hyperthyroidism1. In vitro studies have shown that extracts from bugleweed and lemon balm inhibit stimulation of thyroid hormone production by both TSH and Graves’ antibodies1. An in vivo study in rats showed that oral bugleweed extract alters extra-thyroidal T4 conversion2. Case 1: A 64 year-old woman presented for routine examination and was found to have a TSH of 0.01 mIU/L on 6/6/2016. Labs the next month showed FT4 1.4ng/dL (0.8-1.8) and FT3 4.7pg/mL (2.3-4.2). TSI was elevated to 275% (Normal&lt;140%), consistent with Graves’. She did not have symptoms of hyperthyroidism. The patient’s cat had been treated for hyperthyroidism with Thyrosoothe (TS), a formulation containing extracts from bugleweed and lemon balm. After being diagnosed with hyperthyroidism, the patient began taking TS. On 9/12/16 the patient’s labs were improved with TSH 0.02mIU/L, FT4 0.88 ng/dL (0.8-1.8) and Total T3 86 (76-181). Three months later, the patient’s TSH was 1.89 with normal FT4, Total T3 and TSI. She took TS for 9 months. Her thyroid function tests have remained normal since starting TS, without the need for any other anti-thyroid medications. Case 2: A 46 year-old female presented with periorbital edema in July 2018 and was referred to an ophthalmologist, who diagnosed her with thyroid eye disease. She was also complaining of palpitations and “jitteriness”. She was found to be hyperthyroid on labs and was treated with methimazole (MMI) between August 2018 and February 2019, requiring doses of up to 10mg BID. In March 2019 she stopped MMI due to transaminitis and began taking a thyroid tincture containing bugleweed and lemon balm extract. She has remained euthyroid on the herbal tincture, her transaminitis has resolved, and she has not required any further anti-thyroid medication. Her TSI, which was 0.84 IU/L (Normal&lt;0.55) in May 2019, normalized to 0.36 IU/L in June 2020, after 15 months on this tincture, which she is still taking. Conclusion: In vitro and rat studies of bugleweed and lemon balm extract have demonstrated anti-thyroidal effects. This is the first report of the use of these plant extracts in the treatment of two patients with Graves’ disease, in whom it led to restoration of euthyroidism and normalization of TSI titers. Further study of the anti-thyroidal effects of bugleweed and lemon balm in humans is warranted to evaluate its potential role as an adjunctive therapy in Graves’ disease.References: 1. Auf’Mkolk, M., et al. “Extracts and Auto-Oxidized Constituents of Certain Plants Inhibit the Receptor-Binding and the Biological Activity of Graves’ Igs*.” Endocrinology, vol. 116, no. 5, May 1985, pp. 1687–93. 2. Winterhoff, H., et al. “Endocrine Effects of Lycopus Europaeus L. Following Oral Application.” Arzneim. Forsch., vol. I, no. 44, 1944.

Cumulative Effects of Thyroid Hormones Over 10 Years and Risk of General and Abdominal Obesity

We aimed to assess if changes in thyrotropin (TSH) and free thyroxine (FT4) over 10 years of follow-up would be associated with changes in body mass index (BMI) and waist circumference (WC) or risk of obesity. We enrolled 2317 out of 4179 participants in Tehran Thyroid Study with serum TSH between 0.1–10 mU/l and without history of thyroid medication or surgery. Serum concentrations of FT4 and TSH were measured at baseline and three follow-ups (1999–2011). To account for within-subject correlation, the generalized estimating equation was used to assess the association between one standard deviation(SD) change in the main exposures [cumulative excess (CE)TSH and CEFT4] and changes in BMI and WC; calculated scores of CETSH and CEFT4 were included in models as time-varying exposures. Cumulative excess of TSH or FT4 was not associated with increased incidence of general or abdominal obesity. However, CEFT4 was negatively associated with BMI only in overweight and obese subjects. In GEE analysis, one unit increase in TSH was associated with 0.02 kg/m2 increase in BMI (95% CI: 0.01, 0.03), which remained significant only in women; although the association was not significant after adding FT4 to model. One unit increase in FT4 was associated with 1.5 kg/m2 decrease in BMI (95% CI:−1.8,−1.2) and 4.1 cm decrease in WC (95% CI:−5.1,−3.1) in both sexes independent of TSH and other confounders. Cumulative excess of TSH or FT4 indicated no risk for general or abdominal obesity. However, FT4 was negatively associated with BMI and WC independent of TSH.

Thyroid disease is associated with higher age-related macular degeneration risk: results from a meta-analysis of epidemiologic studies

Background: Although epidemiologic studies have suggested that thyroid disease may be a risk factor for age-related macular degeneration (AMD), this finding is still controversial. Objectives: The aim of this meta-analysis was to investigate whether an association exists between thyroid disease and medication and AMD in epidemiologic studies. Methods: We searched PubMed, EMBASE, and Google Scholar from their inception to March 2020 for cross-sectional, case-control and cohort studies that assessed thyroid function and AMD risk. Data from selected studies were extracted, and a meta-analysis was performed using fixed-effect or random-effect models. The statistical heterogeneity (I2) among studies and the possibility of publication bias were evaluated. If I2 > 50%, a significant heterogeneity existed among studies and a random effects model was used to calculate the pooled RR. Otherwise, a fixed-effects model was performed. Results: A total of 13 epidemiologic studies that consisted of 7 thyroid disease and 7 thyroid medication studies were included. Statistically significant heterogeneity was observed in the study results (I2 thyroid disease = 80.1%, I2 thyroid medication = 69.0%). A significant positive association was found between thyroid disease and AMD, with an overall relative risk (RR) of 1.25 (95% CI: 1.02, 1.54). However, there was no statistical association between thyroid medication and AMD risk (pooled RR 1.26 [95% CI 0.92-1.72]). Egger’s test indicated that there was no significant publication bias for thyroid disease (P=0.889) or thyroid medication (P = 0.226). Conclusions: Our findings indicate that thyroid disease is associated with higher AMD risk. Thyroid disease prevention strategies may have a significant effect on the prevention of AMD and warrant further evaluation.