Jovanovska Mishevska, Sasha

Preferred name

Official Name

Jovanovska Mishevska, Sasha

Main Affiliation

misevskas@medf.ukim.edu.mk

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Case report on a switch from hypothyroidism to hyperthyroidism
(The Endocrine Society, 2023-01-18)
Todorova, Biljana
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Stevcevska, Aleksandra
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Hashimoto's thyroiditis and Graves’ disease are the most common autoimmune thyroid conditions and are more common in women than in men. Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves’ hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes.The most common scenario is the evolution from Graves’ disease (GD) to Hashimoto's thyroiditis (HT), whereas the switch from HT into GD seems to be less common. 53-year-old woman presented with a several month's history of tiredness, cold intolerance and hoarseness in October 2020. She was diagnosed with autoimmune hypothyroidism and achieved euthyroid status following treatment with Tbl. Levothyroxine a 50 mcg S. 1×1. This almost stable status was interestingly interrupted after 9 months (January 2021) when the patient on a regular checkup got laboratory results that showed suppressed TSH levels and a high fT4. The substitution therapy was discontinued immediately. The ultrasound of the thyroid gland showed nonspecific changes: hypoechoic, inhomogeneous gland without any markable pathological formations. The patient was feeling tired, she had palpitations, sweating that is not connected to a physical activity, shaking of the hands and uncontrolled movements of the extremities and neck. Her hair started to fall rapidly in the past few months. She was given Tbl. Metoprolol a 100 mg S.1×1 and Tbl ASA a 100 mg S. 1X1.In October 2021, the new laboratory results showed TSH <0.005 mU/l; fT4 =33.36, aTP-O= 22.77 iU/ml thyroglobulin =46,62, Calcitonin=2.99, Vit. D3=27.3, TSH receptor antibodies= 15.40. Antithyroid therapy was required, and she was given Tbl Thiamazole, Tbl. Propronalol because of the developed clinically and laboratory confirmed hyperthyroidism. There were oscillations in the thyroid status in the first months after the switch to hyperthyroidism, and in December 2021 there was a discontinuation of the Thiamazole treatment for one month because of the unstable TSH level, but afterwards from January 2022 the therapy is administered again and the patient is so far clinically stable under regular control. The patient is feeling good. Conclusion:This rare switch from a state of hypothyroidism to a state of hyperthyroidism is not very common in the clinical endocrinology practice, but should not be missed or misdiagnosed. Suspicion should be raised in the very first moment of tapering the levothyroxine doses in any patient with diagnosed HT during a regular follow up. Our recommendation is doing the TRABs (if available) at the moment of lowering the levothyroxine doses along with the regular laboratory tests of fT4, TSH, ATP-O. If there are any TRABs elevated, the leading way is to think and manage the possible and probable onset of hyperthyroidism
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The effect of thyroid substitution therapy on serum lipids in patients with a mild form of subclinical hypothyroidism
(Publicidad Permanyer, SLU, 2023-02-23)
Velkoska Nakova, Valentina
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Todorova, Biljana
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Background: Overt hypothyroidism and severe subclinical hypothyroidism (ScH) are associated with dyslipidemia, and its condition is reversible after levothyroxine therapy (L-T4). Objective: We investigated the differences in lipids between patients with a mild form of ScH and healthy subjects, and the effect of L-T4 on lipid parameters in ScH group. Materials and methods: Fifty-seven patients with newly diagnosed ScH with thyroid-stimulating hormone (TSH) levels below 10 mIU/L and 30 healthy subjects were included in the study. Lipid parameters were evaluated at the first visit in both groups, and after 5 months euthyroid stage in patients with ScH. Results: Average value of TSH in patients with ScH was 8.1 ± 1.9 mIU/L. At the baseline, the ScH patients had a significantly higher total cholesterol, low-density lipoprotein (LDL-C), and non-high-density lipoprotein (non-HDL-C) levels, and lower HDL-C than the control group. Thyroid substitution therapy in the ScH group significantly decreased total cholesterol and LDL-C, and increased HDL-C. TSH positively correlated with total cholesterol (r = 0.147, p < 0.05). The effect of the L-T4 on lipid parameters was more pronounced in patients with positive thyroid antibodies. Conclusion: In a small sample, mild form of ScH is associated with hypercholesterolemia, which is reversible after L-T4 therapy. Large prospective studies should confirm these results.
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KLINEFELTER SYNDROME AND OTHER SEX CHROMOSOMAL ANEUPLOIDIES IN THE REPUBLIC OF NORTH MACEDONIA
(Macedonian Association of Anatomists, 2022-05-04)
Plaseski, Tosho
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Mihajlovska, Dzuliana
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Markovic-Temelkova, Snezana
Chromosomal anomalies are frequent in male infertility with an incidence of 5.8%, higher than the incidence in general fertile population of 0.5%. Klinefelter syndrome (47, XXY) is the most common disorder of sex chromosomes in humans found in 11% of patients presenting with azoospermia and in 0.7% of patients presenting with oligozoospermia. Boys with 47,XXY are indistinguishable from other boys with normal karyotypes and are often detected when they are evaluated for infertility later in life. Other sex chromosomal anomalies occur less frequently in infertile men.It is considered that many of the 47, XYY men are fertile and this aneuploidy occurs rarely among infertile men. Cases of 46, XX males have also been reported. Molecular analysis shows that most of the 46, XX men have a translocation of the SRY(sex-determining gene) from the Y chromosome on the X chromosome. In our study we analysed the karyotypes of infertile men and identified 39 infertile men with sex chromosomal aneuploidies and Y chromosome micro-deletions. Most of 39 patients had Klinefelter syndrome (31/39 or 79.5%), 4 men had 46,XYY syndrome and 4 had 46,XX syndrome. All detected cases of chromosome aneuploidies were confirmed by cytogenetic analysis.
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Impact of hormone replacement therapy on hyperandrogenicity and glucose homeostasis in postmenopausal women with diabetes
(Medical Faculty, Ss Cyril and Methodius University in Skopje, 2016)
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Temelkova Markovikj, Snezana
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Severe hyponatremia as presenting symptom of small cell lung carcinoma
(The Endocrine Society, 2023-01)
Stevchevska, Aleksandra
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Todorova, Biljana
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A 62-year-old female patient was admitted to ICU in our clinic with symptomatic severe hyponatremia with complaints of fatigue, vertigo, paresthesia of upper extremities and three episodes of loss of consciousness in the past month. She had been hospitalized two weeks before in neurology clinic because of the same symptoms. CT of the brain, EEG, ophthalmology examinations were negative. She did not complain of hemoptysis, cough, weight loss, fever, chest pain or dyspnea. Nephrologist was consulted and renal origin of the hyponatremia was excluded, before admission. Initial laboratory tests were glucose:5,47 umol/L,sodium:109 mEq/L,potassium;4.5 mEq/L,urea 3,9 umol/l;creatinine:52,7 mol/l,calcium:1,22umol/L,TSH 5;Cortisol 819nmol/L;ACTH:16,34 pg/ml. Her medical history included hypertension, primary hypothyroidism and history of smoking. Upon laboratory findings of low serum osmolality, high urine osmolality, high urine sodium levels and clinical euvolemia, and in the absence of renal, pituitary disfunction, adrenal insufficiency, inappropriate ADH syndrome was diagnosed and initially was treated with 3% NaCl. Since this treatment had no effect, it was started with fluid restriction, per os sodium intake was increased and therapy with loop diuretic was initiated, which resulted in correction of the hyponatremia. For the etiology consideration of inappropriate ADH syndrome CT of the thorax was performed, which revealed a neo infiltrative process with atelectasis in the poster basal segment of the left lobe. Histopathological sampling from the biopsy of the mass revealed small cell carcinoma of the lung. Metastasis were not detected. Since basal morning cortisol level was above upper range, with inappropriate measurements of ACTH constantly above 15 pg/ml, additional tests for ectopic Cushing syndrome were done. Overnight 1mg dexamethasone suppression test showed absent suppression of the morning cortisol values of 656nmol/L and ACTH of 22,14 pg/ml and absent circadian rhythm of cortisol secretion, with high measurements of midnight serum cortisol of 652 nmol/L. Diagnosis of ectopic Cushing syndrome and SIADH as part of paraneoplastic syndrome in small cell lung carcinoma was made. It is to be noted that patient had no significant symptoms or signs of hypercortisolemia.</jats:p> <jats:p>We report here a case of small cell carcinoma of the lung whose first presentation was with symptomatic hyponatremia as a result of inappropriate ADH syndrome. The most common neoplasms associated with hyponatremia are various forms of lung cancer. Because of the aggressive nature of the disease, the most common manifestation of small cell carcinoma of the lung is a metastatic one. Therefore, identifying the disease in earlier stages is very important. Unfortunately, these patients have low rates of survival and face a very poor prognosis even with treatment. The presence and early identification of paraneoplastic syndromes can be beneficial in this context.
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A primary adrenal adenomatoid tumor in a young woman
(Bioscientifica, 2014-04-17)
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Jovanovska, Biljana
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Adenomatoid tumors are relatively uncommon neoplasms of mesothelial origin, usually occuring in the male and female genital tracts. Rare extragenital adenomatoid tumor has been identified in adrenal gland. The differential diagnosis includes metastatic carcinoma and adrenocortical carcinoma. We present a case of 30 years old woman with incidentally radiological (ultrasound) finding of unilateral tumor in the right adrenal gland. CT and MRI were of great value in localizing this tumor. The tumor ranged from 5.6 to 6.4 sm in greatest dimension. Clinical and hormonal examinations excluded Sy. Cushing, M. Conn and pheochromocytoma. She underwent a right adrenalectomy using classic laparatomy. The large tumor (d: 8×7×3 sm) was removed and there were no extra-adrenal extension into periadrenal adipose tissue, infiltration of the adrenal cortex or medulla. Histologic examination showed numerous cystic spaces lined by flattened of cuboidal epithelial cells. The small cystic spaces are separated by oedematous fibrovascular stroma with rare epitheloid cells with vacuolated cytoplasm. Immunohistochemical steins were positive for Vimetin(+), s100(+), MCA mesothelial Ag(+), CD 68 (+) and negative for Acitin (−), CK7(−), CD3(−). Conclusions: Adenomatoid tumor is a rare neoplasm that should be added in the differential diagnosis of any adrenal tumor occurring in adrenal gland. The immunohistochemical profile of this adrenal adenomatoid tumor is very supportive of a mesothelial cell origin.
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Adenomatoid Tumor of the Adrenal Gland in Young Woman: From Clinical and Radiological to Pathological Study
(SAGE Publications, 2016-11-17)
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Adenomatoid tumors are neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Extragenital localization sites such as adrenal glands are rare but have been reported. When found in the adrenals, they represent great clinical, radiological and pathological diagnostic challenge, with wide range of differential diagnoses to be considered. We present a case of a 30 years old female, with incidental ultrasound finding of unilateral tumor in the right adrenal gland. Multi slices CT scan was of value in localizing this tumor, but not in the precise diagnosis. The tumor ranged from 5.6 cm to 6.4 cm in greatest diameter. Clinical and hormonal examinations excluded Sy. Cushing, M. Conn and pheochromocytoma. The patient underwent laparoscopic right adrenalectomy. A large tumor (d: 8 × 7 × 3 cm) was removed showing no infiltration of the adrenal cortex or medulla, or extra-adrenal extension into the periadrenal adipose tissue. Histological examination showed numerous cystic spaces lined by flattened cubical epithelial cells. The small cystic spaces were separated by edematous fibrovascular stroma with rare epithelial cells with vacuolated cytoplasm. Immunohistochemical staining was positive with vimentin (+), S100 (+), MCA mesothelial Ag (+), CD 68 (+) and negative with acitin (-), CK7 (-), CD3 (-). Adenomatoid tumor is a rare benign neoplasm that should be added in the differential diagnosis of any adrenal tumor occurring in adrenal gland. The histological and immunohistochemical profiles of this adrenal adenomatoid tumor are very supportive in reaching the diagnosis of this benign tumor of a mesothelial cell origin, helping to avoid invasive treatment.
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Maternal Lipids May Predict Fetal Growth in Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus Pregnancies
(Macedonian Academy of Sciences and Arts/De Gruyter, 2016-11-01)
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Nakova, Valentina Velkoska
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Serafimoski, Vladimir
During diabetic pregnancy, complex metabolic changes occur in the lipid profile. The aim of the study was to determine the predictive values of maternal serum lipid levels on large-for-gestational age newborns during the third trimester in pregnancies of women with type 2 diabetes mellitus (DM2) and gestational diabetes mellitus (GDM).
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Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women
(ID Design 2012/Scientific Foundation SPIROSKI, 2016-03-15)
Iskra Bitoska
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Insulin resistance (IR) is closely associated with diabetes mellitus. On the other hand, increased visceral fat in menopause is also associated with IR, which makes postmenopausal diabetic women in a big risk for cardiovascular diseases. There are conflicting reports about the effects on hormone replacement therapy (HRT) on IR.
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Point mutation C18R in pre-pro-PTH gene in brother and sister with hypoparathyroidism, Fahr’s syndrome and epilepsy
(MIT Univerzitet Skopje, 2021)
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Lejla Shabani-Misini
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Biljana Todorova
Idiopathic hypoparathyreoidism may be sporadic or familial, and may occur as an isolated defect or as a component of a more widespread disorder, such as autoimmune polyglandular failure type 1 or various developmental abnormalities. Familial isolated hypoparathyreoidism (FIH) can result from several types of genetic alterations, including, mutations in the calcium-sensing receptor (CASR) gene, glial cells missing-2 (GCM-2), G protein a11 (GNA11), or in the PTH gene itself. X-linked recessive hypoparathyroidism, a rare congenital form of hypoparathyroidism has also been described. Here, we report a family, brother and sister, with hypoparathyroidism, Fahr’s syndrome and epilepsy diagnosed in early childhood. The genetic testing proved a rare, point mutation in the PTH gene (C18R) with autosomal dominant inheritance. This is the first reported family from North Macedonia with FIH due to mutation in the PTH gene.

Jovanovska Mishevska, Sasha

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