Handbook

PEDIATRIC SURGERY Update
Vol. 51 No. 05 NOVEMBER 2018
Graves Postoperative Hypocalcemia
Grave s thyrotoxicosis is initially managed with antithyroid blocking agents, followed by

surgery and/or radioiodine therapy. In children if medical therapy fails, total
thyroidectomy is the next treatment of choice. Overall the most common complication
after total thyroidectomy is hypocalcemia or tetany which occurs with a greater
incidence in patients with Graves disease when compared with the same procedure in
children with nodular disease or thyroid cancer. Most cases of postop hypocalcemia are
transient with less than 5% permanent. Several mechanisms for the development of
hypocalcemia in Graves disease after total thyroidectomy are proposed. They include
parathyroid hormone (PTH) insufficiency related to injury, devascularization or
inadvertent removal of the parathyroid glands. Also, increase release of thyrocalcitonin
during gland manipulation. This are not the principal mechanisms of hypocalcemia. The
most principal mechanism of hypocalcemia after Graves thyroidectomy is rapid reversal
of an osteodystrophy that existed before surgery caused by the elevated thyroid
hormone level. Grave s children develop a negative calcium level and loss of bone in
the hyperthyroid state something that is partially reversed with antithyroid blocking
therapy known as recalcification tetany or hungry bone syndrome. When the excess
secretion of hormone is eliminated with surgery the extent of bone restoration will be
replenish with calcium hence lowering the ionized calcium blood levels and causing
symptoms of tetany. With excess hormone there is reduced calcium bowel absorption
in addition to bone resorption due to osteoclast activation and loss of calcium in the
urine. Also, antithyroid drug therapy causes calcium and vitamin D deficiency. Twofold
increase rate of a negative calcium slope in the first six hours after surgery or very low
iPTH levels (< 10 pg/ml) predicts severe hypocalcemia. Risk factors that enhance the
state of postop hypocalcemia are younger age and obesity. Preoperative calcium
supplementation for Graves children before surgery replenishes calcium body stores
and reduces symptomatic hypocalcemia. Teriparatide (PTH 1-34) therapy in
post-thyroidectomy patients can control and prevent symptomatic hypocalcemia and
reduce hospitalization (THYPOS trial).
References:
1- Yamashita H, Murakami T, Noguchi S, et al: Postoperative tetany in Graves Disease: Important Role of
Vitamin D Metabolites. Ann Surg. 229(2): 237-245, 1999
2- Walsh SR, Kumar B, Coneney EC: Serum calcium slope predicts hypocalcemia following thyroid
surgery. Internat J Surg. 5: 41-44, 2007
3- Shinall MC, Broome JT, Nookola R, et al: Total Thyroidectomy for Grave s Disease: Compliance with
ATA Guidelines may not Always be Necessary. Surgery 154(3): 1009-1015, 2013
4- Chen Y, Masiakos PT, Gaz RD, et al: Pediatric thyroidectomy in a high volume thyroid surgery center:
Risk factors for postoperative hypocalcemia. J Pediatr Surg. 50(8):1316-9, 2015
2
5- Oltmann SC, Brekke AV, Schneider DF, et al: Preventing postoperative hypocalcemia in patients with
Graves disease: a prospective study. Ann Surg Oncol. 22(3):952-8, 2015
6- Palermo A, Mangiameli G, Tabacco G, et al: PTH(1-34) for the Primary Prevention of
Post-thyroidectomy Hypocalcemia: The THYPOS Trial. J Clin Endocrinol Metab. 101(11):4039-4045, 2016
7- Suwannasarn M, Jongjaroenprasert W, Chayangsu P: Single measurement of intact parathyroid
hormone after thyroidectomy can predict transient and permanent hypoparathyroidism: a prospective
study. Asian J Surg. 40(5):350-356, 2017
Non-invasive Thyroid Follicular Neoplasm
Papillary thyroid cancer (PTC) is the most common histologic thyroid cancer in children.
Follicular thyroid carcinoma (FC) is the second most common thyroid cancer in children
occurring less than 5% of the time. FC is associated with TSH elevation, iodine
deficiency areas and radiation exposure. FC is a tumor composed of neoplastic follicles
rather than papilla but with follicular cells showing nuclear features characteristic of
papillary thyroid carcinoma. Two subtypes of FC are recognized: encapsulated or
minimally invasive FTC and widely invasive FC. Encapsulated FC has increased its
incidence during the past 10 years. It is a tumor with an indolent behavior. In 2012 the
National Cancer Institute revised this pathology and determined to call it Non-invasive
follicular neoplasm with papillary-like nuclear features (NIFTP) if it reflected the
following characteristics: follicular growth pattern, lack of invasion, nuclear features of
papillary carcinoma comprising less than 1% of the tumor, absent psammoma
calcifications, the lesion had clonal origin determine by findings a driver mutation
(biologically a neoplasm) and a very low risk of adverse outcome. NIFTP also has a
lack of common somatic mutation like BRAF and/or RAS. Studies have found that
NIFTP has a low recurrent rate over the years, low metastatic rate, can be managed
with lobectomy only obviating the need for completion thyroidectomy and subsequent
radio-iodine therapy. This proposed reclassification will reduce overtreatment of this
condition and the psychological and clinical consequences associate with a diagnosis of
cancer. NIFTP is a surgical disease and its diagnosis can only be rendered upon
excision and depends totally on adequate or entire sampling of the interface between
tumor and its capsule/periphery to exclude invasive characteristics. To ensure a lack of
infiltrative or invasive growth the entire tumor capsule/periphery should be submitted for
histologic evaluation. A diagnosis of NIFTP cannot be rendered using fine needle
aspiration cytology only. Lymph nodes metastasis are incompatible with NIFTP.
References:
1- Zou CC, Zhao ZY, Liang L: Childhood minimally invasive follicular carcinoma: Clinical features and
immunohistochemistry analysis. J Paediatr Child Health. 46(4): 166-70, 2010
2- Nikiforov YE, Seethala RR, Tallini G, et al: Nomenclature Revision for Encapsulated Follicular Variant
of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA
Oncol 2(8): 1023-1029, 2016
3- Baloch ZW, Seethala RR, Faquin WC, et al: Noninvasive Follicular Thyroid Neoplasm with
Papillary-Like Nuclear Features (NIFTP): A Changing Paradigm in Thyroid Surgical Pathology and
Implications for Thyroid Cytopathology. Cancer Cytopathol. 124(9): 616-620, 2016
4- Rossi ED, Mehrotra S, Kilic AI, et al: Noninvasive Follicular Thyroid Neoplasm with Papillary-Like
Nuclear Features in the Pediatric Age Group. Cancer Cytopathol. 126(1): 27-35, 2018
5- Hung YP, Barletta JA: A user s guide to non-invasive follicular thyroid neoplasm with papillary-like
3
nuclear features (NIFTP). Histopathology 72: 53-69, 2018
6- Poller DN, Nikiforov YE: Non-invasive follicular thyroid neoplasm with papillary-like nuclei: reducing
overtreatment by reclassifying an indolent variant of papillary thyroid cancer. J Clin Pathol . 2016 Jul 7. Pii:
jclinpath-2016-203930.
Renovascular Hypertension
Renovascular hypertension (RVH) in children if untreated leads to ischemic

nephropathy, chronic kidney disease, myocardial infarction, stroke and encephalopathy.
RVH is defined as high blood pressure which results from a lesion reducing blood flow
to part or all of one or both of the kidneys associated with alteration in the
renin-angiotensin mechanism. Incidental hypertension in an asymptomatic child is the
most common presentation of RVH. Younger children are more likely to have
neurological sequelae like seizures, left ventricular hypertrophy, congestive heart
failure, lethargy or poor growth. The most common cause of RVH in children is renal
artery stenosis caused by fibromuscular hyperplasia (FMH) and Takayasu arteritis.
Syndromes such as Neurofibromatosis, Williams, tuberous sclerosis and vasculitis
comprised other less common causes of RVH. FMH is a non-atherosclerotic,
non-inflammatory idiopathic angiopathy affecting medium-size arteries. Mid-aortic
syndrome is another etiology of RVH referring to localized narrowing of the distal
thoracic or abdominal aorta involving the renal vessels as well. Diagnosis of RVH
includes Doppler ultrasound, CT-angiography Scan and MRI, though digital
substraction angiography is the gold standard. More than 50% of RVH arterial lesions
are bilateral. Management of RVH entails medical, surgical or endovascular options.
Medical management only has the least opportunity of cure. Surgical management
includes revascularization, bypass or nephrectomy. Endovascular options developed in
the adult population are increasing use in children. This endovascular options include
mainly percutaneous balloon angioplasty. The use of stents is reserved for severe or
recurrent stenosis or management of complications. Open surgical intervention has a
higher rate of cure higher than 70%. Angioplasty is often utilized for short arterial
narrowing while open surgery is used for long diffuse arterial narrowing or complete
occlusion of renal arteries. Residual hypertension is found in one-third of the children
managed surgically or percutaneously. Other postop morbidity includes aortic rupture,
dissection, bleeding, thrombosis and graft stenosis. Management should be
individualized.
References:
1- Lobeck IN, Alhajjat AM, Dupree P, et al: The management of pediatric renovascular hypertension: a
single center experience and review of the literature. J Pediatr Surg. 53: 1825-1831, 2018
2- Lee Y, Lim YS, Lee ST, Cho H: Pediatric renovascular hypertension: Treatment outcome according to
underlying disease. Pediatr Int. 60(3):264-269, 2018
3- Alexander A, Richmond L, Geary D, Salle JL, Amaral J, Connolly B: Outcomes of percutaneous
transluminal angioplasty for pediatric renovascular hypertension. J Pediatr Surg. 52(3):395-399, 2017
4- Chung H, Lee JH, Park E, et al: Long-Term Outcomes of Pediatric Renovascular Hypertension. Kidney
Blood Press Res. 42(3):617-627, 2017
5- Humbert J, Roussey-Kesler G, Guerin P, et al: Diagnostic and medical strategy for renovascular
hypertension: report from a monocentric pediatric cohort. Eur J Pediatr. 174(1):23-32, 2015
4
6- Sandmann W, Dueppers P, Pourhassan S, et al: Early and long-term results after reconstructive
surgery in 42 children and two young adults with renovascular hypertension due to fibromuscular dysplasia
and middle aortic syndrome. Eur J Vasc Endovasc Surg. 47(5):509-16, 2014
*Edited by: Humberto Lugo-Vicente, MD, FACS, FAAP

Professor of Pediatric Surgery, University of Puerto Rico - School of Medicine,
Rio Piedras, Puerto Rico. Director - Pediatric Surgery, San Jorge Childrens
Hospital.
Address: P.O. Box 10426, Caparra Heights Station, San Juan, Puerto Rico USA
00922-0426.
Tel (787)-999-9450 E-mail: titolugo@coqui.net
Internet: http://home.coqui.net/titolugo
PSU 1993-2018
ISSN 1089-7739

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PEDIATRIC SURGERY Update

Vol. 51 No. 05 NOVEMBER 2018

Graves Postoperative Hypocalcemia

Grave s thyrotoxicosis is initially managed with antithyroid blocking agents, followed by

Non-invasive Thyroid Follicular Neoplasm

Renovascular hypertension (RVH) in children if untreated leads to ischemic

*Edited by: Humberto Lugo-Vicente, MD, FACS, FAAP

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