Langenbecks Arch Surg (2014) 399:1077–1081 DOI 10.1007/s00423-014-1228-0
ORIGINAL ARTICLE
Surgical strategy for primary hyperparathyreoidism with thyroid hemiagenesis Cesare Carlo Ferrari & Kerstin Lorenz & Gianlorenzo Dionigi & Henning Dralle
Received: 6 April 2014 / Accepted: 9 July 2014 / Published online: 31 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background Thyroid hemiagenesis is a rare congenital anomaly, and still more rarely associated with primary hyperparathyroidism (pHPT). Due to the embryologic pathways of the thyroid and parathyroid glands, it remains unclear whether or not thyroid hemiagenesis may be linked to ipsilateral parathyroid agenesis, and consequently, surgical strategy for thyroid hemiagenesis associated pHPT (THAP) does not only depend on preoperative localization but also on the thyroid anomaly. Methods Including the present case report, a total of nine cases with THAP retrieved from the literature were reviewed. Seven of nine cases had thyroid hemiagenesis on the left side, three out of nine showed a parathyroid adenoma on the contralateral side to the thyroid hemiagenesis. Conclusions Based on these cases, it can be concluded that the embryologic pathways of the thyroid and parathyroid glands are different, and in cases of THAP, parathyroid C. C. Ferrari : G. Dionigi Division of General, Surgery Ospedale di Circolo, University of Insubria, Via Guicciardini, 21100 Varese, Italy C. C. Ferrari e-mail: [email protected] G. Dionigi e-mail: [email protected] K. Lorenz (*) : H. Dralle Department of General, Visceral, and Vascular Surgery, University Hospital, University of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany e-mail: [email protected] H. Dralle e-mail: [email protected] C. C. Ferrari : G. Dionigi Endocrine Surgery Research Center, Department of Surgical Sciences, University of Insubria (Varese-Como), Via Guicciardini, 21100 Varese, Italy
exploration should follow standard recommendations for pHPT surgery. Keywords Thyroid hemiagenesis . Primary hyperparathyroidism . Embryology . Localization . Pediatric surgery
Introduction Thyroid hemiagenesis is a rare congenital anomaly of the thyroid gland in which one lobe is totally absent. In normal thyroid gland development, there is a double origin from the primitive pharynx with the medial thyroid anlage, and the neural crest with lateral thyroid anlage. Anomalies and variations of thyroid gland development may affect especially medial, lateral or both thyroid anlagen. These comprise ectopic thyroid, thyroid rests, lingual thyroid, thyroglossal duct cysts, the pyramidal lobe, tubercle of Zuckerkandl, and finally non- (agenesis) or inferior (dysgenesis) development [1]. Hemiagenesis is defined as complete unilateral absence of thyroid tissue. Contrary to complete thyroid agenesis with congenital hypothyroidism, hemiagenesis may not be recognized at all. Due to the lack of specific clinical symptoms, the incidence of this condition, when it occurs alone, is still unknown. Hypothyroidism is the most frequent finding in symptomatic thyroid hemiagenesis followed by other endocrine diseases like thyroid autonomous adenoma and parathyroid disease. In regard to etiology of thyroid hemiagenesis, genetic abnormalities associated with impaired thyroid descent and development focus on previously identified transcription factors, namely TTF-1 and TTF-2, PAX-8, and HoxA3, HOXB3, or HOCD3 [2]. Mouse models showed that TTF-1 disruption results in thyroid agenesis and heterogeneous mutation of PAX-8 in thyroid hemiagenesis [3], while TTF-2 regulates TTF-1 and PAX-8, and its disruption is linked to thyroid dysgenesis [4]. Thyroid dysplasia may occur after disruption
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of HOXA3 as regulator of diverse embryonic processes, and failure of ultimobranchial body fusion with the thyroid when HOXB3 or HOCD3 disrupt concurrently with HOXA3, thus all may be considered as influential in atypical thyroid development [1]. However, applicability of these murine findings to the human thyroid development remains to be established. Several studies analyzed various aspects of thyroid hemiagenesis including the association with other diseases [5–8]. One of the rarest findings was coexistence of thyroid hemiagenesis and primary hyperparathyroidism (pHPT) with eight cases reported in the literature up to now [9–16]. This study presents the ninth case of thyroid hemiagenesis combined with primary hyperparathyroidism and provides a review of the literature.
Patient A 15-year-old female patient came to our attention due to general weakness, malaise, and disturbed general condition. Blood exams revealed hypercalcemia (2.78 mmol/l; reference range 2.25–2.75 mmol/l) and upper normal levels of parathyroid hormone (78 pg/ml, reference range 12–88 pg/ml) suggesting primary hyperparathyroidism. Genetic analysis did not show any MEN1-typical mutation in the menin-gene. Ultrasonography showed complete absence of the left thyroid lobe with a normal sized right thyroid lobe and a small isthmus. Thyroid scintigraphy with 49 MBq 99m TcPertechnetate confirmed aplasia of the left thyroid lobe. Ultrasound and parathyroid scintigraphy by MIBI-SPECT with 404 MBq 99mTc-MIBI localized the suspected parathyroid adenoma in the left paratracheal region. Intraoperatively, ahead to surgical exploration internal jugular vein (IJV) blood analysis for quick PTH-assessement was performed on both sides with PTH of 75.6 pg/ml at the right IJV, and PTH of 72.6 pg/ml at the left IJV. Bilateral surgical exploration therefore was performed, and the parathyroid adenoma was localized to the right inferior gland. Neck exploration of the left thyroid bed showed complete absence of the left thyroid lobe (Fig. 1). A small isthmus was present. The left thyrothymic ligament contained a normal inferior parathyroid gland and a cystic lesion with nodular areas. The cystic lesion was not described in the macroscopic analysis of the specimen, most likely in consequence of alteration by formalin or frozen section processing. Microscopic analysis described the specimen as thymic tissue with configuration according to the age of the patient and without significant pathological findings. The left thyrothymic ligament tissue was removed by preserving the lower parathyroid gland. Frozen section showed normal thymic and fatty tissue. The left upper parathyroid was identified in typical position and showed no abnormalities (Fig. 2). On the right side, a normal sized right thyroid lobe was found. The right superior parathyroid gland was normal in
Langenbecks Arch Surg (2014) 399:1077–1081
Fig. 1 Empty thyroid bed in left hemiagenesis
morphology and position (Fig. 3). The right inferior parathyroid adenoma was small (11×5×4 mm) and located inside the upper third of the right thyreothymic ligament (Fig. 4). After removal of the parathyroid adenoma, qPTH declined from 97.2 to
ORIGINAL ARTICLE
Surgical strategy for primary hyperparathyreoidism with thyroid hemiagenesis Cesare Carlo Ferrari & Kerstin Lorenz & Gianlorenzo Dionigi & Henning Dralle
Received: 6 April 2014 / Accepted: 9 July 2014 / Published online: 31 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background Thyroid hemiagenesis is a rare congenital anomaly, and still more rarely associated with primary hyperparathyroidism (pHPT). Due to the embryologic pathways of the thyroid and parathyroid glands, it remains unclear whether or not thyroid hemiagenesis may be linked to ipsilateral parathyroid agenesis, and consequently, surgical strategy for thyroid hemiagenesis associated pHPT (THAP) does not only depend on preoperative localization but also on the thyroid anomaly. Methods Including the present case report, a total of nine cases with THAP retrieved from the literature were reviewed. Seven of nine cases had thyroid hemiagenesis on the left side, three out of nine showed a parathyroid adenoma on the contralateral side to the thyroid hemiagenesis. Conclusions Based on these cases, it can be concluded that the embryologic pathways of the thyroid and parathyroid glands are different, and in cases of THAP, parathyroid C. C. Ferrari : G. Dionigi Division of General, Surgery Ospedale di Circolo, University of Insubria, Via Guicciardini, 21100 Varese, Italy C. C. Ferrari e-mail: [email protected] G. Dionigi e-mail: [email protected] K. Lorenz (*) : H. Dralle Department of General, Visceral, and Vascular Surgery, University Hospital, University of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany e-mail: [email protected] H. Dralle e-mail: [email protected] C. C. Ferrari : G. Dionigi Endocrine Surgery Research Center, Department of Surgical Sciences, University of Insubria (Varese-Como), Via Guicciardini, 21100 Varese, Italy
exploration should follow standard recommendations for pHPT surgery. Keywords Thyroid hemiagenesis . Primary hyperparathyroidism . Embryology . Localization . Pediatric surgery
Introduction Thyroid hemiagenesis is a rare congenital anomaly of the thyroid gland in which one lobe is totally absent. In normal thyroid gland development, there is a double origin from the primitive pharynx with the medial thyroid anlage, and the neural crest with lateral thyroid anlage. Anomalies and variations of thyroid gland development may affect especially medial, lateral or both thyroid anlagen. These comprise ectopic thyroid, thyroid rests, lingual thyroid, thyroglossal duct cysts, the pyramidal lobe, tubercle of Zuckerkandl, and finally non- (agenesis) or inferior (dysgenesis) development [1]. Hemiagenesis is defined as complete unilateral absence of thyroid tissue. Contrary to complete thyroid agenesis with congenital hypothyroidism, hemiagenesis may not be recognized at all. Due to the lack of specific clinical symptoms, the incidence of this condition, when it occurs alone, is still unknown. Hypothyroidism is the most frequent finding in symptomatic thyroid hemiagenesis followed by other endocrine diseases like thyroid autonomous adenoma and parathyroid disease. In regard to etiology of thyroid hemiagenesis, genetic abnormalities associated with impaired thyroid descent and development focus on previously identified transcription factors, namely TTF-1 and TTF-2, PAX-8, and HoxA3, HOXB3, or HOCD3 [2]. Mouse models showed that TTF-1 disruption results in thyroid agenesis and heterogeneous mutation of PAX-8 in thyroid hemiagenesis [3], while TTF-2 regulates TTF-1 and PAX-8, and its disruption is linked to thyroid dysgenesis [4]. Thyroid dysplasia may occur after disruption
1078
of HOXA3 as regulator of diverse embryonic processes, and failure of ultimobranchial body fusion with the thyroid when HOXB3 or HOCD3 disrupt concurrently with HOXA3, thus all may be considered as influential in atypical thyroid development [1]. However, applicability of these murine findings to the human thyroid development remains to be established. Several studies analyzed various aspects of thyroid hemiagenesis including the association with other diseases [5–8]. One of the rarest findings was coexistence of thyroid hemiagenesis and primary hyperparathyroidism (pHPT) with eight cases reported in the literature up to now [9–16]. This study presents the ninth case of thyroid hemiagenesis combined with primary hyperparathyroidism and provides a review of the literature.
Patient A 15-year-old female patient came to our attention due to general weakness, malaise, and disturbed general condition. Blood exams revealed hypercalcemia (2.78 mmol/l; reference range 2.25–2.75 mmol/l) and upper normal levels of parathyroid hormone (78 pg/ml, reference range 12–88 pg/ml) suggesting primary hyperparathyroidism. Genetic analysis did not show any MEN1-typical mutation in the menin-gene. Ultrasonography showed complete absence of the left thyroid lobe with a normal sized right thyroid lobe and a small isthmus. Thyroid scintigraphy with 49 MBq 99m TcPertechnetate confirmed aplasia of the left thyroid lobe. Ultrasound and parathyroid scintigraphy by MIBI-SPECT with 404 MBq 99mTc-MIBI localized the suspected parathyroid adenoma in the left paratracheal region. Intraoperatively, ahead to surgical exploration internal jugular vein (IJV) blood analysis for quick PTH-assessement was performed on both sides with PTH of 75.6 pg/ml at the right IJV, and PTH of 72.6 pg/ml at the left IJV. Bilateral surgical exploration therefore was performed, and the parathyroid adenoma was localized to the right inferior gland. Neck exploration of the left thyroid bed showed complete absence of the left thyroid lobe (Fig. 1). A small isthmus was present. The left thyrothymic ligament contained a normal inferior parathyroid gland and a cystic lesion with nodular areas. The cystic lesion was not described in the macroscopic analysis of the specimen, most likely in consequence of alteration by formalin or frozen section processing. Microscopic analysis described the specimen as thymic tissue with configuration according to the age of the patient and without significant pathological findings. The left thyrothymic ligament tissue was removed by preserving the lower parathyroid gland. Frozen section showed normal thymic and fatty tissue. The left upper parathyroid was identified in typical position and showed no abnormalities (Fig. 2). On the right side, a normal sized right thyroid lobe was found. The right superior parathyroid gland was normal in
Langenbecks Arch Surg (2014) 399:1077–1081
Fig. 1 Empty thyroid bed in left hemiagenesis
morphology and position (Fig. 3). The right inferior parathyroid adenoma was small (11×5×4 mm) and located inside the upper third of the right thyreothymic ligament (Fig. 4). After removal of the parathyroid adenoma, qPTH declined from 97.2 to
