Drug-induced agranulocytosis (clinical observation)

The majority of agranulocytosis cases are caused by drugs, including nonsteroidal anti-inflammatory drugs, antibiotics, antithyroid agents, etc. Here, we report a case of severe agranulocytosis in a 67-year-old woman following nonsteroidal anti-inflammatory therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor. Although metamizole, has been in use since 1922 in the management of postoperative pain, colic pain, cancer pain and migraine, agranulocytosis as a direct side effect of metamizole therapy has been rarely reported. It is important to keep in mind this rare but potentially life-threatening adverse effect of metamizole, when initiating therapy.

Henoch–Schönlein Purpura (IgA Vasculitis) in Association with Thyrotoxicosis

Graves’ disease is the most common cause of hyperthyroidism, which is characterized by thyroid antibodies and the following clinical manifestations: goiter, ophthalmopathy, and pretibial myxedema. On the other hand, Henoch–Schönlein purpura is an IgA-mediated small-vessel vasculitis. Review of the literature showed a relationship between propylthiouracil overdose and the following Henoch–Schönlein purpura (IgA vasculitis) as a side effect. The patient was a 31-year-old woman with a chief complaint of tremor and significant weight loss who contracted pruritic palpable purpura during her disease course. Then, she underwent the treatment of hyperthyroidism by methimazole which intensified her cutaneous lesions. The diagnosis of Henoch–Schönlein purpura (IgA vasculitis) was confirmed after skin biopsy. Finally, she was treated with colchicine, prednisolone, and radioiodine ablation, which caused her lesions to disappear. The temporal priority of pruritic palpable skin lesions to hyperthyroidism treatment with methimazole suggested that Henoch–Schönlein purpura (IgA vasculitis) was related to hyperthyroidism and was intensified by antithyroid agents in this patient.

Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II–IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II–IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II–IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.

The Unusual Late-Onset Graves’ Disease following Hashimoto’s Related Hypothyroidism: A Case Report and Literature Review

Background. The shift of Graves’ disease (GD) to Hashimoto’s disease- (HD-) related hypothyroidism is well established. However, the opposite is rare. This is likely to the loss of critical thyroid mass available for stimulation by thyroid hormone receptor stimulating antibody, making this shift unusual. Herein, we report a young lady with a late shift from HD into GD and present a scoping literature review. Case presentation. We report a twenty-five-year-old lady with a sixteen-year-history of Hashimoto’s-related hypothyroidism stable on levothyroxine. While following in the clinic, she started developing thyrotoxic symptoms in the form of anxiety, weight loss, and palpitation. Physical examination was remarkable for mild exophthalmos. The thyroid function test confirmed hyperthyroidism. Levothyroxine-induced hyperthyroidism was initially suspected; however, the symptoms did not improve despite reducing and stopping levothyroxine. Subsequent workup confirmed the diagnosis of GD. Discussion and Conclusion. This case highlights a unique association that has significant diagnostic and management implications. This shift should be considered when hyperthyroidism persists despite reducing or stopping levothyroxine. The diagnosis is made utilizing antibody titers and radioiodine update scan. While the management depends on the disease’s stage and the treating physician preference, antithyroid agents can be used initially. Following up these patients is essential as the shift can be transient.

Thyrotoxic Periodic Paralysis—A Misleading Challenge in the Emergency Department

Despite its’ life-threatening potential due to cardiac severe dysrhythmia in the context of severe hypokalemia, thyrotoxic periodic paralysis (TPP) often goes unrecognized. Although classically confined to young Asian men, it can occur irrespective of age, sex, and race. We report a short series of three cases of TPP as first presentation of Graves’ disease in a young Caucasian male and in two Caucasian elderly and middle-aged women, respectively. The first patient developed malignant ventricular arrhythmias due to severe hypokalemia and was defibrillated, with recovery after prompt potassium correction and administration of antithyroid agents and propranolol. The other two cases developed persistent hypokalemia despite adequate potassium chloride (KCl) repletion, with slow recovery of motor deficit and serum potassium normalization up to day 5. In the first case, long-term euthyroid state was achieved via total thyroidectomy due to the presence of a suspicious nodule that proved to be malignant. In the other two cases, medical treatment was the choice of therapy for thyrotoxicosis. None experienced recurrent TPP. Thyroid hormone evaluation is mandatory in the presence of hypokalemic paralysis, even in the absence of clinical signs of thyrotoxicosis. If TPP is confirmed, initial therapy should comprise antithyroid drugs and propranolol, besides hypokalemia correction.

Thyroid storm: a case of haemodynamic failure promptly reversed by aggressive medical therapy with antithyroid agents and steroid pulse

Hyperthyroidism is a common metabolic disorder, although its presentation as an endocrine emergency called thyroid storm is rare. Here we review a case of a thyroid storm as the initial presentation of thyrotoxicosis, with multiple organ failure and haemodynamic collapse due to low-output cardiac dysfunction. Quick intervention with aggressive antithyroid therapy, including steroid pulse, and supportive intensive care measures led to an outstanding improvement and full recovery. The present case clearly shows the beneficial impact of initial clinical suspicion resulting in an early diagnosis and intensive therapy. Moreover, it supports the additional role of steroids to aggressive antithyroid strategy in order to control associated deleterious systemic inflammatory reactions.

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Thiouracil Derivatives as Potential Antithyroid Agents

Hyperthyroidism is the result of uncontrolled overproduction of the thyroid hormones. One of the mostly used antithyroid agents is 6-n-propyl-2-thiouracil (PTU). The previously solved X-ray crystal structure of the PTU bound to mammalian lactoperoxidase (LPO) reveals that the LPO-PTU binding site is basically a hydrophobic channel. There are two hydrophobic side chains directed towards the oxygen atom in the C-4 position of the thiouracil ring. In the current study, the structural activity relationship (SAR) was performed on the thiouracil nucleus of PTU to target these hydrophobic side chains and gain more favorable interactions and, in return, more antithyroid activity. Most of the designed compounds show superiority over PTU in reducing the mean serum T4 levels of hyperthyroid rats by 3% to 60%. In addition, the effect of these compounds on the levels of serum T3 was found to be comparable to the effect of PTU treatment. The designed compounds in this study showed a promising activity profile in reducing levels of thyroid hormones and follow up experiments will be needed to confirm the use of the designed compounds as new potential antithyroid agents.

Synthesis of Some Novel Derivatives of 2-(9H-purin-6-ylsulfanyl) Acetohydrazide as Potential Antithyroid Agents

Some novel derivatives of 2-(9<em>H</em>-Purin-6-ylsulfanyl)acetohydrazide were synthesized by reacting it with respective aldehydes in ethanol. The antithyroid effect of these compounds was ascertained <em>in vitro</em> by studying their complexation with iodine spectrophotometrically. <em>In vivo</em>, the hormonal as well as histological variations in male Wistar rats demonstrated significant antithyroid potential (p ≤ 0.05) of these compounds.