Myxedema Psychosis after Levothyroxine Withdrawal in Radioactive Iodine Treatment of Differentiated Thyroid Cancer: A Case Report

Neuropsychiatric symptoms, especially acute psychosis (often referred to as myxedema madness or psychosis), are rare but possible clinical presentations of patients with hypothyroidism. A 42-year-old woman with papillary thyroid carcinoma and recent total thyroidectomy had developed flat affect, paranoid delusion, and visual and auditory hallucination during inpatient admission for elective radioactive iodine treatment. On admission, her history and physical exam did not reveal symptoms and signs of significant hypothyroidism. Other medical causes of acute psychosis were excluded, and the patient was immediately treated with thyroid hormone replacement therapy. Subsequently, her thyroid function normalized, and her psychotic symptoms gradually improved. Although there is a lack of classic signs and symptoms of hypothyroidism, myxedema madness should be recognized as one of the potentially treatable causes of acute psychosis.

Constipation and Syncope

A 43-year-old woman sought care for severe constipation associated with syncopal episodes. Her constipation alternated with explosive diarrhea. Chronic left-sided abdominal pain and severe bloating developed after eating. She was diagnosed with irritable bowel syndrome. After the initial onset of symptoms, nausea, bloating, and intractable vomiting developed. Symptoms were exacerbated by food and were partially relieved with vomiting. She had multiple episodes of bilious, undigested emesis per day. Trials of antiemetics and motility agents provided no substantial relief. She adopted a liquid diet, avoided solid foods, and eventually had a gastrostomy tube placed. She lost at least 15.9 kg over 2 years. Review of systems was significant for generalized fatigue and a burning sensation in her hands and feet. Her medical history was pertinent for Graves disease previously treated with remote thyroid radioablation, and she was now taking thyroid hormone replacement therapy. Neurologic examination findings were normal except for unreactive pupillary light reflexes. A gastrointestinal tract transit study showed persistently delayed colonic transit with mildly delayed gastric emptying. Autonomic reflex screening showed diffuse postganglionic sympathetic sudomotor, severe cardiovagal, and severe cardiovascular adrenergic impairment. Thermoregulatory sweat testing showed diffuse anhidrosis. Creatinine value was mildly increased. The serum was strongly positive for ganglionic (alpha 3) acetylcholine receptor-immunoglobulin G. The findings strongly suggested an autonomic autoimmune polyganglionopathy, with autoimmune gastrointestinal dysmotility as the predominant phenotype. She received intravenous immunoglobulin. She had complete resolution of her previous constipation, nausea, and vomiting. She regained 22.7 kg. Her gastrostomy tube was removed. Repeated gastrointestinal tract transit studies approached normal findings. Repeated autonomic testing and thermoregulatory sweat testing showed improvement. Over several months, the intravenous immunoglobulin dose was tapered. The patient remained asymptomatic for 8 years on long-term immunosuppression with azathioprine, she had a recurrence of her previous symptoms. Repeated gastrointestinal tract transit studies again showed delayed gastrointestinal tract emptying. Another intravenous immunoglobulin course controlled her symptoms, with normalization of gastrointestinal tract transit studies. Autoimmune gastrointestinal dysmotility can manifest as either hypomotility or hypermotility but most often presents as gastroparesis or pseudo-obstruction. Symptoms include nausea, vomiting, bloating, early satiety, diarrhea, constipation, and involuntary weight loss. It can be idiopathic or paraneoplastic. Risk factors for idiopathic cases include personal or family histories of autoimmunity.

Patterns of Thyroid Hormone Prescription in Patients with Bipolar or Schizoaffective Disorder: Findings from the LiSIE Retrospective Cohort Study

The prescription of thyroid hormone replacement therapy (THRT) has increased in the general population; the thyroid stimulating hormone (TSH) threshold to initiate THRT has decreased. It remains unclear whether a similar trend has occurred in patients with bipolar disorder (BD). In this work we explore patterns and trends of prescribing THRT in patients with BD or schizoaffective disorder (SZD) with an observational study and time-trend analysis in the framework of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. In most patients, THRT was initiated for subclinical hypothyroidism. The median TSH at which THRT was started was 6.0 (IQR 4.0) mIU/L and the median free serum thyroxine (fT4) at which THRT was started was 11.8 (IQR 3.9) pmol/L. The median TSH concentration at the start of THRT decreased annually with 0.10 mIU/L (p = 0.047) and was higher in patients treated with lithium than in patients treated with other mood stabilisers (p = 0.02). In conclusion, THRT was typically initiated in the context of mild or absent alterations of thyroid function tests with a decreasing TSH threshold. As THRT is rarely reversed once initiated, clinicians need to weigh up potential benefits and risks when prescribing THRT for subclinical hypothyroidism in patients with BD or SZD.

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Material and Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months; hyperthyroid, n = 50: 23.1 months; hypothyroid, n = 70: 47.9 months; p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months; with, n = 67: 51.3 months; p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months; p = 0.045). Conclusions: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy

AimsAtrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.Methods and ResultsA retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e–02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e–04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).ConclusionHomozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.

Association of Thyroid Hypofunction with Clinical Outcomes after Microvascular Decompression for Hemifacial Spasm

<b><i>Introduction:</i></b> Data regarding the association between thyroid dysfunction and hemifacial spasm (HFS) are limited. We conducted a single-center, retrospective study to investigate the predictive value of thyroid dysfunction in patients with HFS after microvascular decompression (MVD). <b><i>Methods:</i></b> Between July 2004 and January 2015, 156 patients who were tested for thyroid hormones after MVD for HFS were enrolled in the present study. We assessed their detailed history, clinical manifestations, serum thyroid hormone levels, and surgical outcomes. The patients were classified into low and high groups based on thyroid hormone concentrations, and clinical outcomes were evaluated in each group. <b><i>Results:</i></b> In a total of 156 patients with a median follow-up period of 40.9 months, the improvement rate was 87.8%. The patients were classified into low (76, 48.7%) or high (80, 51.3%) groups based on serum thyroxine (T4) levels. There was a difference between the 2 groups in terms of postoperative outcomes following MVD (<i>p</i> = 0.020). There were no differences in the outcomes according to serum tri-iodothyronine (T3) levels as well as other factors associated with the outcomes. <b><i>Conclusions:</i></b> We found that decreased serum T4 levels are associated with poor postoperative outcomes among patients with HFS. Further studies are needed to examine the clinical benefit of thyroid hormone replacement therapy for patients with suboptimal T4 concentrations as well as active thyroid hormone screening for patients with HFS.

Graves’ Disease Presenting After 25 Years of Stable Thyroid Hormone Replacement Therapy

Background: Autoimmune thyroid disease may present with a wide range of symptoms. When the presentation is hyperthyroidism due to Graves’ Disease the symptoms generally subside over the subsequent two years but may recur at any time months to years later. When the initial presentation is hypothyroidism that person usually remains hypothyroid, requiring thyroid hormone replacement therapy for the rest of their life. Clinical Case: 67 year old woman presenting with hyperthyroidism after 25 years of stable dose thyroid hormone replacement therapy (THRT). She recalls being diagnosed with hyperthyroidism in her late 30s. She did not take any medication at that time. She is very clear that she was not treated with radioactive iodine or surgery. She recalls presenting with fatigue and weight gain about 2 years later at which time she was initiated on thyroid hormone replacement therapy. After multiple dose changes in the first few years she was stabilized on 90 mg daily of Armour thyroid. After more than 20 years on this dose the hyperthyroid symptoms recurred. Her symptoms persisted after decreasing then, ultimately, stopping the Armour Thyroid. Evaluation for causes of hyperthyroidism revealed the presence of both TRAb and TSI antibodies that have decreased in titer but are now still present more than 4 years after the diagnosis of hyperthyroidism. Symptoms have been controlled over this time period with low dose (5-10 mg/day) methimazole. Conclusion: Hypothyroidism is very common in women, with Hashimoto’s Thyroiditis as the usual etiology. When patients on thyroid hormone replacement therapy (THRT) present with symptoms of hyperthyroidism they are usually managed with dose reduction. However, complete cessation of THRT is unusual, especially after more than 10-20 years of therapy. Dose reduction of more than 50% without contributing factors such as significant weight loss should prompt measurement of TRAb and/or TSI to evaluate for Graves’ Disease regardless of the duration of the THRT.