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434 L.S. Wu et al.
Definition
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor diameter 2
cm or less limited to the thyroid
T1a Tumor diameter 1
cm or less limited to the thyroid
T1b Tumor diameter 1–2
cm limited to the thyroid
T2 Primary tumor diameter >2–4
cm
T3 Primary tumor diameter >4
cm limited to thyroid or with minimal extrathyroidal extension
T4a Tumor of any size extending beyond thyroid capsule to invade soft tissues, larynx, trachea,
esophagus, recurrent laryngeal nerve (moderately advanced)
T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels (very advanced)
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
N1a Metastases to level VI (pretracheal, paratracheal, prelaryngeal/Delphian lymph nodes)
N1b Metastases to unilateral, bilateral, contralateral cervical or superior mediastinal lymph nodes
Mx Distant metastases not assessed
M0 No distant metastases
M1 Distant metastases
Stage
Papillary or follicular Medullary Anaplastic
Age <45 years Age >45 years Any age Any age
I Any T, any N, M0 T1, N0, M0 T1, N0, M0
II Any T, any N, M1 T2, N0, M0 T2, N0, M0
T3, N0, M0
III T3, N0, M0 T1, N1a, M0
T1, N1a, M0 T2, N1a, M0
T2, N1a, M0 T3, N1a, M0
T3, N1a, M0
IV
A T4a, N0, M0 T4a, N0, M0 T4a, any N, M0
T4a, N1a, M0 T4a, N1a, M0
T1, N1b, M0 T1, N1b, M0
T2, N1b, M0 T2, N1b, M0
T3, N1b, M0 T3, N1b, M0
T4a, N1b, M0 T4a, N1b, M0
B T4b, any N, M0 T4b, any N, M0 T4b, any N, M0
C
Any T, any N, M1 Any T, any N, M1 Any T, any N, M1
Source: Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL, The original source for this material is the AJCC
Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media, LLC,
http://www.springerlink.com
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Ta b l e 34.8 American Joint Committee on Cancer (AJCC) pathologic-tumor-node metastasis (pTNM) system
lesions will prove to be carcinomas. The diagnosis of carcinoma is confirmed by the finding of capsular and vascular
invasion on permanent histology. Detection of macroinvasion
necessitates completion of thyroidectomy. Indications for
total thyroidectomy include obvious extension of the lesion
through the thyroid capsule, lesions greater than 4 cm (50–
80% prove to be malignant), and contralateral nodularity or
pathology. Follicular carcinoma is associated with a 10-year
survival of 85% and 20-year survival of 70% [70]. Like pap-
illary and follicular malignancies, Hürthle cell carcinomas
produce thyroglobulin, a useful marker for postoperative surveillance. However, Hürthle cells are not iodine-avid; therefore, surgical resection is the mainstay of treatment.
In patients with papillary or follicular thyroid cancer,
postoperative ablation with
131
I is used more frequently to
eliminate residual thyroid tissue in order to decrease the risk
of locoregional recurrence as well as to facilitate long-term
surveillance with radioiodine scans. Several retrospective
studies have demonstrated a significant reduction in the rates
of disease recurrence and disease-associated mortality
[70, 83]. In order to effectively administer postoperative
RAI, the patient must be sufficiently hypothyroid as shown
by elevated serum TSH levels. Levothyroxine is withheld or
withdrawn for 4–6 weeks to maximize thyrotropin stimulation of the remaining thyroid tissue. The resulting hypothyroidism is tolerated poorly by some patients, and it may be
attenuated by administration of liothyronine sodium to
ensure a shorter duration of hypothyroidism. Recently,
administration of recombinant human thyrotropin (rhTSH)
has been used in lieu of traditional thyroid hormone withdrawal.
43534 Surgical Disorders of the Thyroid in the Elderly
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CASE STUDY RESOLUTION
JK’s medical and surgical teams discussed the risks and
benefits of total thyroidectomy with the patient, and the
decision was made to proceed with surgery given the
apparent aggressive nature of her cancer. Given her subjective hoarseness, indirect laryngoscopy was performed,
and her vocal cord function was deemed to be intact; she
had mild reflux. Appropriate medical and cardiologic
clearance was obtained. The patient met with anesthesiology preoperatively. Her warfarin was stopped 5 days prior
to surgery, as was her vitamin supplement. Total thyroidectomy with en bloc resection of the right strap muscle
was performed, along with a right central lymph node
Successful remnant ablation with
131
I was equivalent after
thyroxine withdrawal compared to rhTSH stimulation when
the thyroxine therapy was stopped 1 day prior to the rhTSH
injections and restarted the day following RAI [84–86].
Treatment for medullary thyroid cancer generally includes
total thyroidectomy and central lymph node dissection. An
ipsilateral or bilateral modified radical neck dissection is
performed for lateral cervical lymph node disease. Tumor
debulking may be helpful in alleviating diarrhea and flushing. Nutmeg oil, a combination of atropine sulfate and diphenoxylate hydrochloride, or subcutaneous somatostatin
analogue has offered some relief from symptoms of metastatic disease [71]. Postoperatively, calcitonin remains a
highly sensitive tumor marker and may remain elevated in
patients who present with bulky disease. Preoperative basal
calcitonin levels can individualize the extent of surgery and
postoperative follow-up intervals. On multivariate analysis,
preoperative basal serum calcitonin levels >500 pg/ml best
predicted failure to achieve biochemical remission, followed
by nodal metastasis and need for reoperation. Patients with
nodal or distant metastases did not achieve biochemical
remission when their preoperative basal calcitonin levels
exceeded 3,000 pg/ml. Nodal metastasis emerged at basal
calcitonin levels of 10–40 pg/ml, while distant metastases
and extrathyroidal growth appeared with basal calcitonin
levels of 150–400 pg/ml [87]. Despite this, some patients
with medullary thyroid cancer survive for many years with
minimal symptoms despite significant tumor burden.
Chemotherapy is poorly effective in the management of
locally advanced and metastatic medullary thyroid cancer,
and the role of radiation therapy is questionable. The best
results are achieved in familial medullary or MEN II kindreds where patients can be identified presymptomatically
and appropriately treated [55, 71]. More recently, tyrosine
kinase inhibitors have been shown to inhibit RET tyrosine
dissection. The patient did well postoperatively; she had
no evidence for change in voice or hypoparathyroidism.
Her warfarin was restarted on postoperative day 1, and she
was discharged home that day with follow-up with her
cardiologist later in the week. Her final pathology revealed
multifocal papillary thyroid cancer. The largest focus
measured 4.1 cm in the right lobe, and an additional 5 mm
focus was identified in the contralateral lobe.
Lymphovascular invasion was seen, and there was extension of tumor into soft tissue, but surgical margins were
negative. Three of ten lymph nodes were positive for metastatic disease, giving her an AJCC pT4aN1aMx, or stage
IVA, papillary thyroid cancer. She met with endocrinology regarding adjuvant RAI therapy.
kinase activity. Clinical studies are underway, but only preliminary results have been published [88, 89].
Anaplastic thyroid cancer most often is advanced at presentation, and it usually presents in the 6–7th decades of life.
It is almost always unencapsulated and invades surrounding
structures. Cervical lymphadenopathy and pulmonary metastases are common. It does not concentrate iodine or express
thyroglobulin [90]. Although there is no satisfactory treatment for anaplastic cancer, local control can be attempted
with palliative surgery, chemotherapy, or radiotherapy.
Tumor debulking, tracheostomy, and feeding gastrostomy
may be required for palliation [91]. In the rare instance of
early anaplastic carcinoma localized to the thyroid, total thyroidectomy has resulted in long-term survival [92].
Primary non-Hodgkin’s lymphoma of the thyroid is most
common in elderly women, occurring most often in the background of autoimmune thyroid disease. Primary thyroid lymphoma usually is not a surgical disease, although surgeons
often assist by obtaining adequate tissue to establish a diagnosis and determine tumor markers. Use of multimodality
chemotherapy, particularly with anthracycline agents, and
external radiotherapy results in dramatic tumor shrinkage
and rapid resolution of airway compromise. The overall
5-year survival is approximately 70%, depending on stage
and histologic type [71, 75, 93].
Conclusion
Thyroid disease is common in the elderly. In this population,
the clinical manifestation of thyroid dysfunction can be subtle,
often hidden by a background of coexistent disease. Hypo- and
hyperthyroidism often are subclinical, and therapeutic decisions
may be dictated by patients’ preference and overall health
436 L.S. Wu et al.
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status. The incidence of thyroid nodules increases with age, as
does the risk of thyroid malignancy and the aggressiveness of
the thyroid tumor. Surgery is the mainstay of treatment for thyroid cancer. Quality-of-life issues related to voice, swallowing,
and calcium metabolism are especially salient in elderly
patients. Thyroid surgery in this population is associated with
increased attendant risk, but it can be performed safely, especially in the hands of high-volume thyroid surgeons. It is
imperative that internists, geriatricians, endocrinologists, and
thyroid surgeons work together as an interdisciplinary team to
formulate and tailor treatment strategies.
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Chapter 35
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Parathyroid Disease in the Elderly
Leslie S. Wu, Sanziana A. Roman, and Robert Udelsman
CASE STUDY
An 82-year-old woman was brought to the Emergency
Department with a 5-day history of worsening lethargy
and confusion. From prior hospital records, her past
medical history was notable for two episodes of nephrolithiasis, gastroesophageal reflux disease, and hypertension. Her medications included hydrochlorothiazide,
metoprolol, omeprazole, and aspirin.
Physical examination revealed a frail-appearing
woman, who was arousable to voice, and oriented only to
person. She was afebrile and normotensive, but mildly
tachycardic with a heart rate of 100 beats per minute.
Neurologic exam was nonfocal. The remainder of her
Introduction
The primary function of the parathyroid glands is to maintain
calcium homeostasis through the secretion of parathyroid
hormone (PTH). This hormone is regulated by serum calcium
through calcium-sensing receptors (CaSRs) on the parathyroid
cell surface. In turn, most peripheral tissues, primarily kidney
and bone, have PTH receptors which can affect varying functions. In the past, disturbances in this system were difficult to
recognize until the development of clinically significant
disease. With the development of better biochemical assays
for serum PTH and calcium levels, subclinical derangements
can be diagnosed before patients become symptomatic.
The
management of patients with the broad spectrum of
metabolic calcium disturbances remains controversial.
L.S. Wu (*)
Department of Surgery, Maine Medical Center, 887 Congress Str,
Suite 400, Portland 04102, ME, USA
e-mail: miniwuwu@gmail.com
examination was significant only for poor skin turgor
and dry mucous membranes.
Laboratory studies were notable for a normal white
blood cell count, mild hemoconcentration, blood urea
nitrogen (BUN) 25
serum calcium 14.7 mg/dL, and albumin 4.3 g/dL.
Urinalysis was negative.
The patient was admitted to the hospital with hypercalcemia. She was hydrated appropriately with intravenous crystalloid fluids, with subsequent improvement of
her mental status and calcium level. Additional laboratory evaluation was obtained, revealing an intact parathyroid hormone (iPTH) level of 200 pg/ml. The patient was
diagnosed with primary hyperparathyroidism.
mg/dL, serum creatinine 1.3 mg/dL,
Mineral Homeostasis
Plasma calcium exists in three phases: protein-bound, ionized,
and complexed. Normally, approximately 1 g of inorganic calcium is absorbed daily in the proximal small intestine. About
45% of total blood calcium is protein-bound, predominantly to
albumin, but also to globulins. A similar fraction is ionized.
The rest is complexed to organic ions such as citrate, phosphate, and bicarbonate. Calcium is in constant flux between
the extracellular and intracellular spaces, in bone, and in renal
glomerular filtrate, which is reabsorbed by the normal kidney.
The ionized fraction of serum calcium controls vital
cellular functions, such as neuromuscular transmission,
muscle contraction, and blood clotting. Precise maintenance of calcium concentration within a very narrow range
in extracelluar fluids is therefore critically important.
The
binding of calcium to albumin is pH-dependent,
increasing with alkalosis, and decreasing with acidosis.
Thus, if the ionized calcium is low, acidosis tends to protect an individual from manifesting the symptoms and
signs of hypocalcemia; conversely, alkalosis predisposes a
patient to symptomatic hypocalcemia.
R.A. Rosenthal et al. (eds.), Principles and Practice of Geriatric Surgery,
DOI 10.1007/978-1-4419-6999-6_35, © Springer Science+Business Media, LLC 2011
439
440 L.S. Wu et al.
Negative feedback
Parathyroid glands
Sense low serum
calcium and increase
PTH secretion
Bone
Releases calcium
and phosphate
Skin
Vitamin D
Parathyroid
hormone
Calcitriol
1,25(OH)
2
D
Increased
serum calcium
Liver
Kidney
Increases calcitriol
formation and decreases
calcium excretion
Small intestine
Increases absorption
of dietary calcium
Calcidiol
25-OH-D
Calcitriol
1,25(OH)
2
D
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Fi g u r e 35.1 Calcium
metabolism.
The adult body contains approximately 700 g of phosphate, primarily located in the teeth and bones. Plasma levels
of calcium and phosphate are inversely related, and the
primary agents responsible for calcium metabolism are PTH,
vitamin D, and calcitonin (see Fig. 35.1) [1].
Parathyroid Hormone (PTH)
The chief cells of the parathyroid gland constantly monitor
ionized calcium concentrations through their cell surface CaSR,
thus allowing the circulating level of PTH to change within
seconds after an alteration in serum calcium [2]. PTH secretory
rates are related to serum ionized calcium and 1,25-dihydroxyvitamin D by an inverse sigmoidal relationship. Low ionized calcium concentrations maximally stimulate secretion,
while increases in calcium suppress the production and release
of PTH. PTH secretion is exquisitely sensitive to very small
alterations in the calcium concentration, which have substantial
effects on the rate of hormone synthesis and release.
PTH is synthesized within the parathyroid gland as a
115-amino-acid precursor molecule (preproPTH) that is successively cleaved within the cell to form the mature 84-aminoacid PTH. This form of the hormone is packaged into
secretory granules and released into the circulation. Mature
PTH is metabolized in the liver into the active N-terminal
and inactive C-terminal fragments. The intact molecules and
N-terminal fragments have half-lives of approximately
3–5 min, while the inactive C-terminal fragments have a
half-life of hours. The C-terminal fragments are excreted by
the kidneys, and usually accumulate to high levels in the
serum of patients with renal failure.
PTH inhibits osteoblasts and stimulates osteoclasts. In the
kidney, PTH causes a decrease in calcium clearance as well
as increased renal excretion of phosphate by inhibiting its
reabsorption in the tubules. In addition, PTH stimulates
hydroxylation of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, which allows for enhanced calcium absorption in
the proximal intestine [3].
Vitamin D
The sterol 1,25-dihydroxyvitamin D, or calcitriol, is an essential mediator of calcium homeostasis. Calcitriol synthesis
begins with ultraviolet activation of 7-dehydrocholesterol in
the skin, generating cholecalciferol (vitamin D). In the liver,
vitamin D is readily hydroxylated to 25-hydroxyvitamin D2,
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which in turn is hydroxylated to the potent calcitriol. This
final step occurs in the kidney and is tightly regulated by PTH.
In turn, calcitriol has a regulatory effect on PTH, by exerting
a physiologic inhibition of the parathyroid glands [4].
Calcitonin
Parafollicular, or C cells, of the thyroid gland secrete the
peptide hormone calcitonin. Calcitonin interacts with receptors in kidney and bone. The primary function of calcitonin
is to lower serum calcium, and this hormone is released
rapidly in response to hypercalcemia. It inhibits osteoclastic
bone resorption and quickly blocks the release of calcium
and phosphate from bone. Ultimately, this effect, along with
the inhibition of resorption, leads to a fall in serum calcium
and phosphate [3]. The physiologic effect of calcitonin in
humans, however, is very modest.
Hypercalcemia
The most common reason for the finding of hypercalcemia in
an elderly patient, in the oupatient setting, is primary hyperparathyroidism (HPTH), while hypercalcemia in the inpatient
population often is secondary to malignancies. Diagnosing the
correct etiology requires careful clinical evaluation of patients,
as well as serologic and biochemical testing (Table 35.1) [5].
After a thorough history and physical examination,
laboratory measurements of fasting serum calcium, PTH,
creatinine, and vitamin D levels should be performed to determine if the hypercalcemia is parathyroid-mediated (in which
serum PTH levels are elevated inappropriately) or nonparathyroid-mediated (in which serum PTH levels are suppressed appropriately). Normally, functioning parathyroid cells
abruptly cease PTH release when the surrounding extracellular fluid calcium concentration is elevated. Therefore, in cases
in which hypercalcemia results from a non-parathyroidmediated condition, serum PTH levels will be suppressed [6].
Ta b l e 35.1 Differential diagnosis of hypercalcemia
Parathyroid-mediated Non-parathyroid-mediated
Primary hyperparathyroidism
Parathyroid
adenoma (85%)
Parathyroid
hyperplasia (15%)
Parathyroid carcinoma (<1%)
Secondary/tertiary
hyperparathyroidism
Familial hypocalciuric
hypocalemia
Lithium therapy
Source: Modified and reproduced from [
Malignancy-associated hypercalcemia
Local osteolytic hypercalcemia
Humoral hypercalcemia of malig-
nancy (PTHrP and calcitriol)
Granulomatous disease (sarcoidosis
and tuberculosis)
Endocrinopathies (hyperthyroidism
and adrenal insufficiency)
Drugs (thiazides, vitamin D and
calcium)
Immobilization
1]
Non-Parathyroid-Mediated Hypercalcemia
This category includes conditions in which patients have
hypercalcemia and serum PTH levels that are suppressed
appropriately; the parathyroid cells perceive excess extracellular calcium concentrations, and markedly reduce their
hormonal release. Cancer is the most frequently diagnosed
etiology of non-PTH-mediated hypercalcemia, particularly
in the hospitalized population. This malignancy-associated
hypercalcemia is classified into two primary forms, osteolytic and humoral.
The second form of malignancy-associated hypercalcemia is local osteolytic hypercalcemia, which occurs when a
neoplasm directly invades the bony skeleton, resulting in
localized destruction and calcium release. In contrast to
malignant humoral hypercalcemia, local osteolytic hypercalcemia does not involve the elaboration of systemically active
products. Rather, it appears to result from the production or
local stimulation of bone-active cytokines as well as other
osteoclast-activating factors. This form of pathologic hypercalcemia is most commonly associated with multiple
myeloma; however, it has also been linked to adenocarcinoma of the breast and certain lymphomas [7].
Humoral hypercalcemia of malignancy results from the
systemic effect of a circulating factor produced by the neoplasm.
Most commonly, the factor involved is parathyroid hormonerelated protein (PTHrP), a peptide that has been shown to
recapitulate most of the metabolic effects of PTH, including
stimulation of bone turnover and alteration in renal handling of
both calcium and phosphate [7]. In humans, PTHrP serves as
an important paracrine factor in may tissues, including skin,
bone, breast, the central nervous system, and the vasculature.
Neoplasms that elaborate PTHrP include squamous cell carcinomas (naso- and oro-pharynx, larynx, lung, esophagus, and
cervix), adenocarcinoma of the breast and ovary, bladder transitional cell carcinoma, T-cell lymphomas, renal cell carcinoma, and carcinoid tumors. The other factor that may cause
malignant humoral
associated with B-cell lymphomas [7, 8].
There are other benign, non-PTH-mediated causes of
hypercalcemia encountered in the elderly. These include
medications and supplements, such as thiazide diuretics
and excess exogenous calcium, vitamin D, or vitamin A.
Granulomatous diseases, such as sarcoidosis and tuberculosis, are associated with hypercalcemia through the direct
production of calcitriol. In addition, several endocrinopathies
are associated with hypercalcemia, including hyperthyroidism with augmented bone turnover, pheochromocytoma with
PTHrP production, and adrenal insufficiency linked with
decreased calcium clearance. Rarely, hypercalcemia may
result from prolonged immobilization, particularly in settings in which bone turnover is already stimulated, such as
recovery from fractures or surgery [3].
hypercalcemia is calcitriol, which is often
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Parathyroid-Mediated Hypercalcemia
The differential diagnosis of parathyroid-mediated hypercalcemia includes HPTH, familial hypocalciuric hypocalcemia
(FHH), and lithium therapy. The remainder of this chapter will
focus primarily on the forms and treatment strategies of HPTH.
However, FHH and lithium therapy briefly are discussed below,
as the differences between these diagnoses are important.
FHH, also known as benign familial hypercalcemia, is an
inherited autosomal dominant condition resulting from a
deactivating mutation in the extracellular CaSR [9]. In this
condition, the cell surface receptor is sub-normally activated
by extracellular calcium. In the face of mild elevation of
serum calcium, PTH levels are inappropriately normal or
slightly elevated. However, urinary calcium excretion is
reduced, due to the same defective CaSRs in the nephron,
with subsequent increased urinary calcium reabsorption.
Although FHH is classified as parathyroid-mediated, since
PTH secretion is abnormal, it is a unique condition and distinct from the more common primary HPTH. Generally, it is
diagnosed in younger patients with asymptomatic, mild
hypercalcemia. The family history usually identifies affected
relatives. It does not require surgical intervention, as parathyroidectomy will not cure the condition.
Chronic lithium therapy may increase serum calcium levels with inappropriately normal or mildly elevated PTH concentrations. Lithium appears to alter the sensitivity of the
CaSR, thus increasing the set-point of extracellular calcium
concentration. However, parathyroid adenomas and multigland hyperplasia have also been described in patients chronically treated with lithium [10]. Distinguishing those patients
with drug-induced hypercalcemia from those with mild primary HPTH can be challenging.
Hyperparathyroidism
Hyperparathyroidism was first recognized during the 1920s
and was thought to be a relatively uncommon condition,
presenting usually as nephrolithiasis or as a complication
of severe bony demineralization [5]. With the application of
multiphasic blood testing revealing elevated serum calcium
concentrations and the availability of accurate PTH determinations, HPTH now is recognized to be a more common
disorder, particularly in the elderly population.
Primary Hyperparathyroidism
Primary hyperparathyroidism is the most common form of
HPTH and is the most frequent explanation for hypercalcemia
in the outpatient setting. Population-based estimates reveal an
overall incidence of approximately 25 per 100,000 in the general population with about 50,000 new cases occurring
annually. The peak incidence is in the fifth to sixth decade of
life, with a female to male ratio of about 3:2. Some studies
estimate the overall prevalence of HPTH in the elderly at
2–3%, with approximately 200 cases/100,000
The most common clinical presentation is that of asymptomatic, or minimally symptomatic, mild hypercalcemia.
Primary HPTH generally is caused by a benign, solitary
parathyroid adenoma in 80–85% of patients. In about 5% of
patients, two distinct adenomas (“double adenoma”) are
found. Multigland parathyroid hyperplasia is present in
15–20%. In younger patients, this may be associated with
familial syndromes, such as multiple endocrine neoplasia
(MEN) types I and IIA. Patients with MEN-I have enlargement and hyperfunction of all parathyroid glands, whereas
patients with MEN-IIA may have asymmetric parathyroid
gland enlargement. The rare hyperparathyroidism-jaw tumor
syndrome is another autosomal dominant inherited condition
presenting with early-onset primary HPTH and fibro-osseous,
cystic jaw neoplasms [
dromes are rare in the elderly patients, but certain mutations
may manifest later in life, therefore in the appropriate clinical
setting, MEN needs to be considered even in elderly patients.
Parathyroid carcinoma is a rare cause of primary HPTH,
accounting for less than 1% of cases. In contrast to benign
HPTH, it occurs equally in men and women. Patients with
parathyroid carcinoma present most often in the fifth and
sixth decades of life. Longstanding untreated primary HPTH
may devolve into parathyroid carcinoma, which may then
present in the elderly patients [14]. Although these tumors
are slow-growing, they have a high propensity to recur
locally, and recurrent disease is difficult to eradicate. Patients
with recurrent and metastatic disease often suffer from
severe, debilitating hypercalcemia, control of which may
involve palliative surgical resection and the use of drugs,
including bisphosphonates and calcimimetics, to lower the
serum calcium level [
Clinical and Diagnostic Evaluation
With the advent of routine serum calcium screening, the typical presentation of primary HPTH has changed from a
severe, debilitating illness to a disease with subtle symptoms
and physiologic derangements. Common signs include nephrolithiasis, nephrocalcinosis, osteopenia, and osteoporosis
(Table 35.2) [17]. Hypertension is frequently present in
patients with primary HPTH, and a variety of mechanisms
have been proposed to explain this relationship. It appears to
be most closely correlated with the degree of renal impairment seen in patients with hypercalcemia. However, one
12, 13]. Index cases of MEN syn-
15, 16].
population [11].
Ta b l e 35.2 Symptoms and associated conditions in patients with primary
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hyperparathyroidism
Symptoms
Weakness, exhaustion, and fatigue
Bone pain, back pain, and joint pain
Polyuria, nocturia, and polydipsia
Loss of appetite, nausea, and dyspepsia
Memory loss and depression
Associated conditions
Weight loss
Bone fracture, joint swelling, and gout
Nephrolithiasis, hematuria from passage of renal calculus
Gastric ulcer, duodenal ulcer, and pancreatitis
Hypertension
study found that parathyroidectomy led to a substantial fall
in both systolic and diastolic pressures in 54% of hypertensive
subjects that appeared to be unrelated to improvement in
renal function [18]. Most endocrine specialists do not believe
that curative surgery in primary HPTH is associated with a
significant improvement in hypertension.
There are many subtle abnormalities associated with
primary HPTH, including decreased cognitive function,
depression, lethargy, myalgias, arthralgias, constipation, and
urinary symptoms, such as increased thirst and urinary
frequency. Petersen performed psychiatric examinations on
54 patients with primary HPT and detected mental disturbances in more than 50% [19, 20]. However, it is often
difficult to prove that these nonspecific findings result from
primary HPTH because they are common in the elderly. In a
general population cohort study of over 4,000 individuals,
Schram et al. found that serum calcium levels that were at the
upper range of normal or frankly elevated were associated
with faster decline in cognitive function, particularly for
patients over the age of 75 years [21].
The diagnosis of primary HPT typically is made by biochemical evidence of an elevated serum calcium concentration, usually in conjunction with an elevated serum intact PTH.
Approximately half of patients with primary HPTH have
hypophosphatemia. However, in the presence of significant
renal impairment, serum phosphate levels may be elevated.
Because of the effect of PTH on bicarbonate excretion in the
kidney, patients with primary HPTH often have a hyperchloremic metabolic acidosis [
13]. Approximately 10–40% of
HPTH patients have elevated levels of alkaline phosphatase,
which indicates some degree of increased bone turnover.
Although osteitis fibrosa cystica, the classic form of parathyroid bone disease, is rarely seen today, even patients with mild
disease can be seen to have biochemical or histologic evidence
of bone involvement. Dual-energy X-ray absorption (DEXA)
scanning of the lumbar spine, hip, and forearm has become the
standard method for assessing bone density to diagnose osteoporosis in the setting of primary HPTH [22–24].
44335 Parathyroid Disease in the Elderly
Fi g u r e 35.2 Parathyroid adenoma. Sagittal ultrasound shows a para-
thyroid adenoma (white arrows) behind the lower pole of the right
thyroid lobe (black arrows).
Patients with FHH must be distinguished from those with
primary HPTH. This can be done with a 24-h urinary calcium
excretion study, which is uniformly low in the setting of
FHH. In contrast, patients with primary HPTH have a
normal or elevated 24-h urinary excretion of calcium [9].
Postmenopausal women often have hypercalciuria for several
years after the onset of menopause from estrogen decrease,
therefore increased urinary calcium levels in this population
may not always be due to hyperparathyroidism.
Although rare, parathyroid carcinoma should be suspected in
patients who demonstrate a rapid and sustained rise in both their
serum calcium and PTH levels. A palpable neck mass sometimes may be appreciated [25, 26]. A parathyroid adenoma is
rarely, if ever, palpable on physical examination. Rather, this
neck mass is more likely to represent a thyroid nodule.
There have been extensive discussions regarding the use
and availability of preoperative imaging studies in patients
with primary HPT. In the past, patients who had not undergone previous surgical exploration did not require any radiographic localization studies other than finding an experienced
parathyroid surgeon. However, the increased use of minimally invasive parathyroidectomy techniques has mandated
preoperative imaging.
Imaging studies can be sorted into noninvasive and invasive techniques. The noninvasive studies include the following: nuclear medicine scans, such as methoxyisobutylisonitrile
(sestamibi) studies, which can be combined with single photon emission computed tomography (SPECT) imaging;
ultrasound (Fig. 35.2); computed tomography (CT) scans;
and magnetic resonance imaging (MRI). The noninvasive
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