Endocrinology 119

MEDICINE AND ALLIED

ENDOCRINOLOGY

Chapter 1
DIABETES MELLITUS
Sharad Kumar, S K Sharma
Definition: Traditionally the term Diabetes has been
defined as a metabolic disorder of multiple etiologies,
characterized by chronic hyperglycemia together with
disturbances of metabolism of carbohydrates, lipids and
proteins resulting from insulin deficiency, resistance or
both.
The term Diabetes mellitus however does not represent a
single disease entity but rather a set of disease states that
share certain characteristics, most important of them is
hyperglycemia.
Classification of Diabetes: Currently the classification
suggested by the Expert Committee in 1997 is the one
mostly used
1. Type 1 Diabetes-
 Autoim
mune
 Idiopat
hic
2. Type 2 Diabetes
3. Gestational Diabetes
4. Other specific types
–quite rare
Table1: Clinical features of type 1 and type 2 diabetes
mellitus
Type 1 Diabetes: Patients affected by it, are usually
females and may be of any age, but typically present in
the first or second decades of life. With a relatively short
history, and a rapidly deteriorating course, if left
unrecognized and untreated these girls quickly go into
diabetic ketoacidosis and even coma. The diagnosis in
such young girls is often missed until urine is detected to
have ketones, which is pathognomonic of it’s diagnosis.
These patients are insulin deficient and therefore
Endocrinology 121
1
critically require exogenous insulin for survival through
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out their lives. The broad guidelines of their management
remain the same, as for the much commoner type 2
diabetes, except for the fact that insulin secretagouge are
ineffective in them.
Type 2 Diabetes: It represents the most common form of
Diabetes. Currently in India we have about 50.8 million
people affected with it. Unfortunately out of these about
50% of them are unaware of its presence and out of these
who receive treatment only 50% do get it properly
treated.
Etiology of Type 2 Diabetes: The exact etiology is still
not known. Two factors, however can be broadly
implicated in its genesis.
(a)
Genetic factors-The predisposition to diabetes is a
genetic factor. It is evident from the fact that it
occurs in up to 91% of co twins. Further a very high
prevalence in certain ethnic groups, which can not
be accounted for by other environmental factors,
also points in this direction.
(b)
Acquired factors-Several studies have proved that the
incidence of Diabetes, as well as of obesity, shoots
up in the migrant population, which has migrated
from rural agrarian life style to affluent urban
lifestyle. So presence of obesity, along with a
sedentary lifestyle, is a very important risk factor for
the development of diabetes.
Pathophysiology and Natural History of Diabetes:
Evidence indicates that the persons, who evolve to get
type 2 Diabetes, start with increasing insulin resistance.
To overcome this, the beta cells keep on increasing the
production of Insulin and keep the blood glucose levels
in the normal range. At certain stage, usually several
years later, the beta cells fail to increase the production
of insulin any further. It is at this stage that the blood
glucose starts rising and the person is said to have
become diabetic. Even at this stage, initially the insulin
production can be further increased through the help of
insulin secretagouge and other oral agents, to keep the
blood glucose levels under control. After several, usually
approximately 10 years after the diagnosis of diabetes,
the beta cells fail to respond any further to this increased
 122 Textbook of Family Medicine
whipping by Sulphonylureas. It becomes impossible at
this stage to control glucose levels even with the
maximal doses of oral anti diabetic drugs. At this stage,
the person is labeled to have developed secondary
1 sulphonylurea failure, needing insulin therapy.
Clinical features: Several trials have proved that about
half of the persons having Diabetes are unaware of its
presence and it gets detected either accidentally or when
the person is being investigated for some other reason.
The classical triad of polyphagia, polydipsia and
polyurea also in some persons sometimes leads to its
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suspicion leading to investigations. In some others, a
persistent weakness, unintentional weight loss, a
persistent genital or other infection or the detection of
ants at the toilet seat, leads to suspicion.
Diagnosis: Since the diagnosis has a wide range of
implications stringent criteria must be satisfied.
Table 2: Diagnosis of Diabetes Mellitus
Diabetes
Fasting plasma glucose >126mg/dl
and/or
2 Hour post glucose load > 200mg/dl
plasma glucose
Impaired glucose tolerance -(IGT)
Fasting plasma glucose and <126mg/dl
2 hour post glucose load
Plasma glucose. 140 to 200mg/dl.
Impaired fasting glycemia (IFG)
Fasting plasma glucose 100-125 mg/dl
And (if measured)
2 hour post glucose load, <140 mg/dl
Plasma glucose.
All values refer to venous plasma glucose. Capillary
plasma glucose values would be the same fasting but
about 18 mg/dl (1 mmol/l) higher than venous levels,
after the glucose load. The glucose load is 75 g
anhydrous glucose.
Complications of Diabetes:
Chronic Complications: The chronic microvascular
complications of Diabetes include retinopathy,
nephropathy and neuropathy. To reduce the impact of
these complications, the management strategies include
regular surveillance for early detection of complications,
and tight glucose control, for both primary prevention
and secondary intervention as demonstrated in DCCT
trial.
Macrovascular disease as manifested by cerebrovascular,
peripheral vascular and coronary artery disease is a
major chronic complication of diabetes. Regular
surveillance and management of cardiovascular risk
factors is essential.
Acute Complications: In uncontrolled state, the
metabolic decompensation can lead to deterioration of
consciousness or even to coma. In type 1 diabetes, the
accumulation of acetoacetate and beta hydroxy butyrate
in blood can be severely cardio toxic, and this diabetic
ketoacidosis (DKA), needs urgent treatment, preferably
in the ICU setting.
In type 2 diabetes, although the levels of ketone bodies is
not often very high, but the amount of dehydration is
often severe and dangerous. In fact the mortality in this
nonketotic hyperosmolar coma, could be as high as 10
%.
The broad principles of treatment in both the cases are
almost the same. Since it is the dehydration and
associated electrolyte imbalance which has the potential
to be the killer, rather than hyperglycemia, the priority is
to rapidly correct the dehydration, by rapid infusion of
normal saline. Slow continuous IV plain (soluble) insulin
needs also to be given simultaneously, by an insulin
pump if facilities are available. The third important
ingredient to be given is Potassium, always diluted in the
IV bottle and never in bolus.
Once the blood glucose approaches to about 250mg/dl,
the IV fluid is usually changed to 5% dextrose saline,
rather than normal saline, with continued insulin. This IV
infusion is than continued till the patient starts eating
again. Needless to say that these patients need intensive
and continuous monitoring, especially of their blood
glucose, urinary / blood ketones and electrolytes, besides
other routine ICU parameters.
Table 3: Complications of diabetes mellitus
Acute complications
Diabetic ketoacidosis (DKA)
Hyperglycemic hyperosmolar state (HHS)
Chronic complications
Microvascular
Retinopathy
Neuropathy
Nephropathy
Macrovascular
Coronary artery disease
Cerebrovascular disease
Peripheral vascular disease
Non-vascular
Gastrointestinal (gastroparesis, diarrhea)
Genitourinary
Dermatologic
Infectious
Cataract and glaucoma
Miscellaneous (multiple etiology)
Diabetic foot
Erectile dysfunction
Management of Diabetes Mellitus:

The management of a diabetic patient can be discussed
under the following heads –
Investigations: Since about 50% of the diabetic persons
are unaware about their diabetic status, it should be
assumed that his blood sugar has remained high for quite
some time. The protocol to be followed, therefore, is that
his all the target organs, including a detailed ophthalmic
examination, should be got assessed at the time of
diagnosis and thereafter every one year. In many centers
the investigations carried out at the time of diagnosis,
include a fasting and post prandial blood glucose, A1c,
liver and renal function tests, a fasting lipid profile, ECG
and a urinary microalbumin creatinine ratio.
Patient Education: Since it is a chronic disorder which
affects the entire life of the person, and the family,
detailed counseling of the patient and the entire family is
a must, which may require several sessions. The
important points that need be covered are –
 That it is a disorder
to be taken care of, for the entire life.
 Necessity of regular
treatment and monitoring.
 Necessary changes in
the life style.
 Ability to recognize
and manage hypoglycemia
 What to do in any
sickness- the sick day schedule.
Life Style Modifications: Because it is extremely
difficult to expect sudden and dramatic changes in any
body’s life style, following a brief meeting of few
minutes, it is recommend to keep on hammering the
salient features in each meeting.
Diet: Probably no other aspect of the management of
diabetes leaves patients, as well as physicians more
confused than this. Further, the haunting memories of the
by gone era, of severe restrictions for all diabetic
patients, leaves the patients more afraid of the diabetic
diet, rather than diabetes itself. Fortunately in the modern
era of evidence based medicine, the diabetic patient’s
diet need to be not excluding several things but should be
inclusive of most things.
The advice should be given aiming for
1. Achieving the
ideal body weight for height and body frame.
2. Distribution of
carbohydrates, through out the day, to avoid
hypoglycemic episodes.
3. Avoiding day to
day changes in meal timings.
4. Make the meals
balanced, as far as the micronutrients and dairy
products are concerned.
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5. Eat healthy food
to decrease risks of atherosclerotic diseases.
Exercises: Exercises are good for a diabetic or for that
matter any other person, as they improve glycemia, body
weight, cardiovascular fitness, insulin sensitivity,
strength in the lean tissues of the body, help prevent rise
1
in blood pressure, besides improving the flexibility of the
musculoskeletal system, and increasing the sense of well
being.
In general isotonic exercises are better than isometric
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exercises for achieving all the said benefits. To achieve
the full benefit, these should be carried out fairly
regularly, that is, without gaps of more than 48 hours
between the two sessions. As a rule of thumb a session of
brisk walking for twenty minutes, preceded and followed
up, by a five minute each, period of warm up and cool
down phase respectively. For the full advantage, the pace
of these walking sessions should be such that the person
becomes unable to speak to the fellow walker, without
getting breathless.
Strength training, by the help of weight lifting is also
recommenced for the maximal benefits. Again as the
metabolic memory does not last for more than 48 hours,
so each session should not be after a gap of more than 48
hours. The current recommendations are, for a set of
eight sessions, each, consisting of ten repetitions.
Precautions in Exercise: Over enthusiastic exercise can
also be sometime risky, and certain precautions must also
be emphasized. In general, an unaccustomed person
should be warned about the possible risks and counseled
accordingly. Certain more important risks could be.
1. Precipitating a
cardiovascular event –Preventive check up
2. Accelerated
hypertension - Prior control
3. Retinal hemorrhage
– Prior optimal management
4. Ketoacidosis –Proper
prior control of glycemia
5. Limb injuries-
Accepting the limitations
Pharmacotherapy: As on date several drugs in the
following major groups are available with us.
1) Insulin sensitizers with predominant action in the
Liver-Biguanides:
Table 4: Oral glucose lowering agents
 124 Textbook of Family Medicine

about six weeks.

The most troublesome side effect that it produces is
fluid retention and weight gain. Over all, however, it
tends to retard the process of atherosclerosis,
1 through advantages in serum lipids and of it’s
anticoagulant properties. Recent observations about
an increased incidence of fractures with it’s use, has
however given a jolt to its clinical utility. Though the
most optimum dose used is 30 mg /day, in a single
dose, now a days a low dose of 7.5 mg/ day is also
being increasingly used, as it has been seen that
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while it reduces blood glucose values significantly,

produces only minimum edema and weight gain.
Place: As an isolated agent or with Metformin in the
initial stages of Diabetes, or as an "add on" therapy
when the maximal doses of Sulphonylurea fails to
elicit the desired response. It can also be combined
with all the other antidiabetic molecules.
3) Insulin Secretagouge:

All insulin secretagouge act by binding to

Out of the two agents originally available Phenformin
use has now been abandoned because of the risk of lactic
acidosis. Though the risk of this complication exists with
Metformin also, but is practically zero, if certain
precautions are observed. It’s use should be avoided in
case there is an associated renal /hepatic/cardiac/or
respiratory failure. To be specific it should not be used, if
the serum creatinine value is, or more than 1.5mg/dl in a
male or more than 1.4 mg/dl in women.
Thiazolidinediones have gone out of favour for treatment
of diabetics as they increase the risk of heart failure and
osteoporosis. Rosiglitazone has already been withdrawn
and pioglitazones are to be used with caution. DPP IV
inhibitors be used as 2nd or 3rd line agents.
The UKPDS data shows that it does reduce the incidence
of micro as well as macro vascular complications.
Though it can be given up to 2550 mg /day, the doses
should be gradually up titrated, starting from 500to 1000
mg/day. The only significant side effects are, GI
disturbances which occur in up to third of patient’s, often
necessitating reduction /discontinuation of therapy.
Place: An agent of first choice, especially in an over
weight person, can be combined with molecules of any
other group, doesn’t produce hypoglycemia and weight
gain and may even assist in loosing weight.
2) Insulin Sensitizers with Predominant Action in
the Peripheral Insulin Sensitive Tissues:
Thiazolindinediones: The only available agent in
the market today is Pioglitazone. This drug, again is
a weak agent in itself, and also therefore is incapable
of producing hypoglycemia if given without a
sulphonylurea. The full effect of it comes only after
Sulphonylurea1 (SUR 1) receptors. This SUR1 acts
both as a glucose sensor as well as a trigger for
insulin secretion.
a--Sulphonylureas: Currently available second
generation Sulphonylureas viz. Glipizide,
Glibenclamide (Glyburide), Gliclazide and
Glimepiride are the main antidiabetic agents of use
today. They can be used in up to 20 mg , 20 mg,320
mg and 8mg/day doses, respectively. While
Glipizide, Glibenclamide and Gliclazide are
generally advised to be taken 30 minutes before
breakfast and dinner, Glimepiride can be taken
immediately before breakfast and also the entire
dose can be taken just before breakfast.
Glibenclamide is most potent, and so carries the
maximum risk of hypoglycemia. Along with these, it
must be ensured, that the person takes three regular
carbohydrate containing meals everyday, to prevent
episodes of hypoglycemia. All those persons like
advocates, sales personnel, emergency duty
personnel, like in police service, doctors etc, must be
cautioned against this potentially serious adverse
effect. Such persons who can not take regular meals
should be preferably put on repaglinide or
nateglinide(see below).
Since Type 2 Diabetes is a progressive disease, a
person with recent onset Diabetes, generally
responds to a lower dose, while a person with a
diabetes of several years duration need a larger dose.
When a person fails to achieve normoglycemia, even
with the maximal dose of these agents, along with
other group of oral antidiabetic medications, it is

assumed that secondary beta cell failure has
occurred, and the person now needs insulin for his
blood glucose control.
Place: These are the most potent, and most
commonly used molecules to bring down the
glucose. A normal blood glucose can be maintained
only for few years in a patient with out any one of
these agents. The clinician should be aware of a
possibility of weight gain and allergic reaction (rare)
besides hypoglycemia while prescribing them.
b--Meglitinides: Out of the two available molecules
in this category Repaglinide is the more potent and
more commonly used drug than Nateglinide.
The sole advantage of this group of medications is
that they allow a more flexible routine because of a
shorter duration of action. These patients do not
experience hypoglycemia even if they miss lunch, or
change their meal’s time everyday. This flexibility
however, comes at a cost of more frequent drug
intake, that is, immediately before every meal. Being
potent secretagouge they also carry a potential risk
of hypoglycemia, and hence should be titrated with
the lowest dose of 0.5 mg to 1.0 mg to 2.0 mg per
tab, before each major meal.
Place: For treating patients with moderate
hyperglycemia and fairly advanced diabetes, in
whom the regularity of meals can not be ascertained.
This group has no major interaction or side effects
except hypoglycemia. Like all other groups, these
can also be combined with medicines of other
groups.
4) Alpha Glucosidase Inhibitors: Since these agents
act only locally at the intestinal mucosa, so they lack
systemic actions. These agents block the action of
alpha glucosidase enzyme and hence the digestion of
carbohydrates into glucose is reduced, decreasing
the availability of glucose for absorption. This
undigested carbohydrate, in the gut, thus generates
lots of dyspeptic side effects. The doses of it needs
to be therefore gradually up titrated. Since these do
not stimulate beta cells, they have only a weak anti
hyperglycemic action and also therefore, can not
produce hypoglycemia or weight gain. Acarbose and
Miglitol need to be given, 25 to 100 mg with each
major meal, along with the first bite. The third agent
Voglibose, which is still not available in US, needs
to be given in 0.2 to 0.3 mg, with each major meal.
This agent produces much less dyspeptic symptoms
than Acarbose and Miglitol.
Place: These agents can be used in the early stages
of diabetes, either alone or in combination of
Endocrinology 125
metformin. Later on these can be added if
Sulphonylureas fail and the patient refuses to accept
insulin.
5) DPP IV Inhibitors: Dipeptidyl peptidase is the
enzyme that destroys the insulin very soon after its 1
release. The action of this enzyme is blocked by this
group of molecules. Theoretically these molecules
are the dream products, they are orally active,
weight neutral, carry no need for dose titration, do
not produce hypoglycemia, need to be given once a
MEDICINE AND ALLIED
day (Sitagliptin, Saxagliptin and Linagliptin) or
twice a day (Vildagliptin) and are virtually devoid of
any side effects. Lack of long experience, and the
cost, are the only factors which prevent these from
being the agents of first choice, and lack of good
and potent hypoglycemic effect prevent them from
being the universally prescribed medication.
Place: All patients, who have a recent onset of
diabetes, can be put on it, or else it can be used as an
"add on" therapy, after other agents fail individually
or collectively.
6) Bromocriptine: It can be used alone or, in
combination of other agents, in the dose of 0.8 mg to
4.8 mg / day in a single oral dose given in the
morning. The starting dose being 0.8mg; it can be
increased over a period of several weeks, to its
maximal dose. It has the capacity to control both
fasting and postprandial glucose, via its action on
modulating hypothalamic drive. This agent, however
also is a weak agent only. Though chances of
hypoglycemia with its use are quite remote, the
usual adverse effects like syncope, nausea, and
headache may sometimes be encountered.
Place: Though the experience with it is still limited,
it can be used as a starting agent or as an ‘add on’
therapy to the existing medication in an uncontrolled
overweight patient.
7) GLP -1 Mimetics: GLP 1 is the most important
incretin hormone, secreted from the gut, in response
to oral feeding. These then stimulate insulin
secretion from the beta cells. Given parenterally,
these have the additional benefit of helping in
achieving weight loss. They do not produce
hypoglycemia, but do produce nausea and some
times even vomiting, initially, and hence are started
in lower doses. These can also be combined with
drugs of other classes. Today, the injectable route,
lack of a long experience and the high cost, are the
limiting factors for it’s routine use.
Place: All those patients who are obese, motivated
to loose weight,not afraid of needles and who can
 126 Textbook of Family Medicine
afford it, can be placed on it either alone or in
combination of other molecules.
8) INSULIN: This wonderful agent, which was
1 discovered the first, among all antidiabetic agents, as
early as 1921, is usually discussed in the end.
Traditionally insulin was being sourced from pig
(porcine) and cow (bovine). This being a
polypeptide, is unstable at room temperature and can
not be given orally, as it is digestible by intestinal
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proteases. It is injected subcutaneously by a syringe
or by more easy and comfortable pen devices.
Preparations: The simplest insulin is called
crystalline, soluble, short acting or plain insulin. It is
usually given subcutaneously but is the only insulin
that can be given IV also.
The slightly modified insulin molecule, called NPH
(Neutral Protamin Hagedorn) insulin, has twice the
working duration and is called the intermediate
acting insulin. These are cloudy insulins, have
duration of action lasting up to 18 hours, and can not
be given IV, because these are insoluble, and do get
settled at the bottom of the vial upon standing.
Table 5: Types of Insulin
Modern Insulins: In an endeavor to improve the
quality of control, recombinant human insulins were
introduced in early nineties, after the typical bovine
and porcine insulins, which are still though available
but have become much less popular.
In last two decades certain genetically modified
designer insulins have also been developed. These
insulins are ultra long acting, Glargine and Detemir,
and ultra short acting Lispro, Aspart, and Glulisine.
With experience, they can be used to give still better
control, but at a substantially higher cost, and the
use of them can be left for the specialist.
Schedules: A typical patient basically needs control
of his blood glucose throughout 24 hours. This
includes control of fasting hyperglycemia which is
due to increased hepatic glucose output, and also the
surges in glucose level which follow each meal, that
is breakfast lunch and dinner. The best way to
control these surges would be to give several shots
usually three, to cover three spikes following each
meal and a shot of intermediate acting at the bed
time to take care of the fasting values. This therapy
called basal bolus therapy, however makes a daily
routine of four pricks, which is usually unacceptable
to most patients.
A compromise then generally is made, and a
combination of soluble and intermediate insulin is
injected before breakfast and before dinner. This
schedule of split mixed insulin, with only two pricks
in a day, usually gives a reasonable control
throughout the day. With the availability of
premixed insulins, usually in the ratio of 30% plain
and 70% intermediate, this regimen has become the
most commonly prescribed insulin therapy today.
For other rarer specific cases a combination of 50%-
50%, 25%-75% are also sometimes used.
Dose Adjustments: Because the degree of insulin
resistance varies from patient to patient the
requirement also varies. Frequent monitoring and
careful observation is the key to suitably adjust the
doses in any individual. The schedule most
commonly followed for insulin initiation, is 0.6
units/kg of body weight /day, of a premixed variety,
divided, two thirds before breakfast and one third
before dinner, injected subcutaneously. The response
is usually judged by a fasting and a two hour post
breakfast glucose values, usually after a weeks time.
Then if fasting is high, the evening dose can be
uptitrated or if post breakfast is high, then dose
before breakfast is increased. Usually an increment
of two units is made, unless it is very high, when a
larger increment can be made cautiously.
Adverse Effects of Insulins: Fortunately except for a
hypoglycemic episode, these are very safe. Though
there may be some weight gain, there is no other
adverse effect that is encountered frequently.
Place: The insulin therapy is indicated in the
following situations-
 Type 1 Diabetes – By
definition these patients can not survive without
insulin for more than few days hence they all
require insulin for the rest of their lives.

 Emergencies – Like surgery,
acute sepsis, comatosed patient, organ failure like
renal, hepatic, cardiac or respiratory failure.
 Pregnancy- No oral medicine

can be given.
Beta cell failure- This is the
most common indication in the day to day
practice. Typically about ten years from
diagnosis, most type 2 diabetic patients fail to
respond to maximal doses of Sulphonylurea and
then these are the patients who need insulin on a
regular basis for control of their blood sugars.
Metabolic Targets in Diabetes: Though the targets laid
down in various guidelines (Table 6), hold good for the
majority of patients, generally are not chased for, in
elderly patients, in those who are living alone, or may be
in a remote area or in whom, for other reasons, the life
expectancy is not very good. Further, sometimes
especially in Type 1 patients, achievement of this strict
target may be very difficult. Individualization of the
targets, therefore, assumes great importance for any
patient.
Table 6: Guidelines for Glycemic Targets
DIABETIC KETOACIDOSIS
This is a serious complication seen more frequently in
type 1 DM and less frequently in type 2 DM. DKA is
caused by insulin deficiency often in association with
stress and activation of counter-regulatory hormones.
The stress conditions include infections, trauma,
myocardial infarction and surgery.
The biochemical abnormalities are hyperglycemia,
ketosis, and metabolic acidosis. Hyperglycemia leads to
osmotic diuresis, dehydration and electrolyte loss.
Insulin deficiency and elevated glucagon, growth
hormone and catecholamines lead to increased lipolysis
from adipose tissue and increased synthesis of ketone
bodies in the liver.
Clinical Features
The usual clinical manifestations are nausea, vomiting
and abdominal pain. Patients may have respiratory
Endocrinology 127
distress, shock, confusion and coma. Examination
reveals the presence of dehydration, rapid and deep
breathing (Kussmaul’s breathing), and fruity breath odor.
There may be tachycardia and hypotension.
Investigations
1
Plasma glucose is very high. Arterial blood gas measure-
ment shows metabolic acidosis. Urine examination
reveals positive ketone test. Hyponatremia,
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hyperkalemia, azotemia and hyperosmolality are the
other findings. Urine culture, blood culture, blood counts
and X-ray of chest should be done to detect the evidence
of infections. ECG is performed to rule out cardiac
events.
Management
This is a medical emergency. The patient is hospitalized.
The essential components of treatment are;
1. Intravenous saline is initially given to correct
dehydration. Once blood glucose level falls to
250 mg/dL, the fluid is changed to 5 percent
dextrose solution.
2. Intravenous infusion of regular insulin is
administered until the ketoacidosis is corrected.
3. Potassium and phosphate are replaced as needed.
4. Sodium bicarbonate is generally not required.
However, it is given if blood pH is less than 7.0.
5. Antibiotics are given to treat infections.
6. The electrolytes, blood glucose, blood urea,
serum creatinine, arterial blood gases are
periodically monitored.
HYPERGLYCEMIC HYPEROSMOLAR
STATE (NON-KETOTIC HYPEROSMOLAR
DIABETIC COMA, HHS)
This is characterized by severe hyperglycemia,
hyperosmolality and dehydration without keto-acidosis.
Ketoacidosis is generally absent because residual insulin
secretion is adequate to inhibit lipolysis and ketogenesis.
It is a complication of type 2 DM. The precipitating
factors include stress, infections, drug non-compliance,
stroke, and alcohol. The onset is insidious. The usual
 128 Textbook of Family Medicine

symptoms are polyuria, weight loss, drowsiness, and

altered sensorium. Severe dehydration, hypotension and
tachycardia are the usual clinical findings.
Thromboembolic complications are common.
1 Laboratory findings include marked hyperglycemia
(>600 mg/dL), plasma osmolality greater than 350
mOsm/L, absence of ketonemia, pH >7.3 and prerenal
azotemia. Lactic acidosis may occur in some patients.
MEDICINE AND ALLIED

Treatment includes fluid replacement, insulin therapy,

and management of electrolytes especially potassium and
phosphates. The requirement for insulin is less in HHS
than in DKA.

Chapter 2
THYROID DISORDERS
KVS Hari Kumar
Thyroid disorders are one of the common disorders in the
outpatient department and are seen in 4-5% of the
population. Amongst the functional disorders of thyroid
gland, hypothyroidism (underfunction) is more common
than hyperthyroidism (overfunction). Structural disorders
including thyroid nodule, multinodular goiter and
malignancy account for the majority of other diseases in
practice.
Thyroid gland (Greek thyreos, shield, plus eidos, form) is
located in the lower part of the neck with 2 lobes and
isthmus connecting both the lobes. The thyroid gland is
the only palpable endocrine gland in both sexes. The
gland derives its blood supply from superior and inferior
thyroid branches of external carotid artery and
subclavian artery respectively. The gland secretes two
hormones called thyroxine (T4) and triiodothyronine
(T3). T3 is the primary active hormone in tissues. T 4 has
limited effect directly and is converted to T 3 in peripheral
tissues. The conversion takes place in organs like liver,
brain, heart, and is extremely important for the overall
functioning of the body.
Thyroid hormones are derived from thyroglobulin, a
large iodinated glycoprotein. Iodine is essential for
tyrosine residues on thyroglobulin leading to formation
of T3 and T4. Iodine deficiency is prevalent in many
regions of India and it leads to increased prevalence of
goiter, hypothyroidism and cretinism. The recommended
average daily intake of iodine is 150µg/d for adults, 90–
120µg/d for children, and 200µg/d for pregnant women.
Urinary iodine is >10 g/dL in iodine-sufficient
populations.
Thyroid hormones affect body temperature and
circulation, appetite, energy levels, growth, skeletal
development, muscle tone and agility, cardiac function,
fluid balance, blood sugar levels, central nervous system
function, bowel function, blood lipid levels, and the
regulation of fat, carbohydrate and protein metabolism in
all cells. The gland is under negative feedback control of
pituitary and hypothalamus. Thyroid stimulating
hormone (TSH) is produced from pituitary and the TSH
releasing hormone (TRH) from the hypothalamus.
Thyroid dysfunction due to disease of the thyroid gland
is known as primary and diseases due to pituitary and
hypothalamus are called as secondary and tertiary
respectively.
Endocrinology 129
1
The most common cause of hypothyroidism is an
MEDICINE AND ALLIED
autoimmune condition, called Hashimoto's Thyroiditis.
Other causes are atrophic thyroidits, radioiodine therapy,
radiation thyroiditis, congenital hypothyroidism, iodine
deficiency and hypopituitarism leading to secondary
hypothyroidism. The most common cause of
hyperthyroidism is Graves' Disease. Other causes of
hyperthyroidism are toxic nodule, toxic mutinodular
goiter, subacute thyroiditis, functioning metastasis of
thyroid carcinoma, gestational toxicosis.
CLINICAL EXAMINATION
The examination of the thyroid disorders consists of
examining the thyroid gland and a search for signs of
abnormal thyroid function including ophthalmopathy and
dermopathy. Look for any surgical scars, obvious
masses, lymphadenopathy or distended veins in the neck.
The thyroid can be palpated with both hands from behind
or while facing the patient, using the thumbs to palpate
each lobe and by asking the patient to swallow sips of
water, thyroid consistency can be better appreciated.
Take a note of thyroid size, consistency, nodularity, and
any tenderness or fixation. A bruit over the gland
indicates increased vascularity, as occurs in
hyperthyroidism. In retrosternal extension, the lower
borders of the thyroid lobes are not clearly felt. The
"NOSPECS" scheme is an acronym used to document
eye changes in Graves’ disease:
0 = No signs or symptoms
1 = Only signs (lid retraction or lag), no symptoms
2 = Soft tissue involvement (periorbital edema)
3 = Proptosis (>22 mm)
4 = Extraocular muscle involvement (diplopia)
5 = Corneal involvement
6 = Sight loss
LABORATORY EVALUATION
Thyroid hormones: The initial screening test for any
thyroid disorder is to check for thyroid hormones.
Presence of low TSH with elevated T3 and T4 indicates
thyrotoxicosis and elevated TSH with low T3 / T4 is
diagnostic of primary hypothyroidism. A normal TSH
excludes thyroid abnormality mostly with few exceptions
 130 Textbook of Family Medicine

like central hypothyroidism, thyroid hormone resistance, General

euthyroid sick syndrome. Free thyroid hormone Weakness, tiredness
estimation is useful in situations like pregnancy, Cold intolerance
nephritic syndrome etc. Dry coarse skin
1 Diagnostic aids: Thyroid autoantibodies (TPO) help in Pallor
Hair loss
the identification of autoimmune thyroid disease.
Thyroid stimulating Immunoglobulins are measured in Puffy face, hand, and feet
cases of thyrotoxicosis and they are positive in cases of Myxedema
Graves’ disease. The serum thyroglobulin level is Weight gain, poor appetite
elevated in the presence of functional thyroid tissue and Hypothermia
MEDICINE AND ALLIED

is useful in follow up of thyroid cancer patient. Goiter

Pertechnate scan demonstrates increased uptake in cases Hoarse voice
of Graves’ disease and decreased uptake in destructive
thyroiditis. Ultrasonography is useful in the evaluation of Gastrointestinal
thyroid nodules and thyrotoxicosis. FNAC is helpful in Constipation
identifying the risk of malignancy in a thyroid nodule Large tongue
and determine the treatment decisions.
Reproductive
THERAPY Menorrhagia
Amenorrhea
Hypothyroidism: The daily replacement dose of Infertility
levothyroxine is usually 1.6µg/kg body weight (typically Galactorrhea
100–150µg). Lower doses (25 – 50 µg) are sufficient for
Nervous system
subclinical hypothyroidism. Elderly individuals, patients
Poor memory
with ischemic heart disease need small doses initially
and gradual uptitration. The dose is adjusted on the basis Poor concentration
of TSH levels, to be done every 3 months initially and at Carpal tunnel syndrome
a yearly interval on stable therapy. Clinical response Delayed relaxation of deep reflexes
starts after 2 weeks and it takes around 10 weeks for Cardiovascular
complete response. The causes of increased
Bradycardia
levothyroxine requirements are malabsorption (celiac
disease, small-bowel surgery), estrogen therapy, and Hypertension
drugs that interfere with T4 absorption. Ischemic heart disease
Pericardial effusion
Hyperthyroidism: It is treated by reducing thyroid
hormone synthesis, using antithyroid drugs, or reducing
the amount of functioning thyroid tissue with radioiodine Box 1. Subclinical Thyroid Dysfunction
or thyroidectomy. The main antithyroid drugs are
propylthiouracil, carbimazole, and methimazole. All Subclinical Hypothyroidism
inhibit the function of thyroid peroxidase, thereby Definition: Presence of elevated TSH with normal free
reducing oxidation and organification of iodide. thyroid hormone levels is known as subclinical
Propylthiouracil also inhibits peripheral deiodination of hypothyroidism. The presence or absence of symptoms is
T4 to T3. The initial dose of carbimazole or methimazole not relevant to diagnosis.
is usually 10–20 mg every 8 or 12 h, and propylthiouracil Indications for levothyroxine: Presence of goiter,
is given at a dose of 100–200 mg every 6–8 h. dyslipidemia, irregular menstrual bleeding, infertility,
Propranolol (20–40 mg every 6 h) is helpful to control recurrent abortions, positive TPO antibodies.
adrenergic symptoms, especially in the early stages.
Maximum remission is seen at 18 – 24 months and in Subclinical Hyperthyroidism
resistant patients definite ablative therapy using surgery Definition: Presence of suppressed or low TSH with normal
or radioiodine is recommended. Radioiodine therapy is free thyroid hormone levels.
contraindicated in patients of Graves’ disease with active Indications for antithyroid drugs: Presence of atrial
opthalmopathy. fibrillation, osteoporosis, dyslipidemia, irregular menstrual
bleeding, infertility, old age, prolonged subclinical
hyperthyroidism.
Causes of hypothyroidism
Table 1: Clinical features of hypothyroidism

Primary hypothyroidism
Spontaneous atrophic
Post-thyroidectomy
Following 131I administration for hyperthyroidism
Congenital
Goitrous
Hoshimoto’s thyroiditis
Iodine deficiency
Drug induced (lithium, amiodarone, methimazole)
Genetic enzyme defects (dyshormonogenesis)
Secondary hypothyroidism
Destruction of pituitary gland
Post-surgery
Post-radiation
Tumor
Disorders of hypothalamus
Box 2. Congenital Hypothyroidism
Clinical clues: prolonged jaundice, feeding difficulty,
lethargy, constipation, macroglossia, hypothermia,
edema, delayed closure of fontanelle and umbilical
hernia.
Identification: cord blood sample at delivery or heel
prick sample after 48 hrs
Investigations: High TSH (> 20 mIU/L), low T4 in
primary hypothyroidism and low T4 with normal or
low TSH in secondary hypothyroidism
Management: Start early to prevent permanent
neurological damage. Higher doses of levothyroxine
initially @ 15 – 20 µg/kg/day, adjust based on TSH
value every 3 months
Box 3. Pregnancy and Thyroid disorders
Hypothyroidism: In a patient of hypothyroidism,
advise to continue the levothyroxine, throughout
pregnancy. The dose needs to be increased by 25 –
50% due to increased demand in pregnancy. Monitor
TSH every 2 months during pregnancy and aim to
keep the TSH in gestation specific range.
Hyperthyroidism: It is preferable to use
propylthiouracil in Ist trimester. Propylthiouracil and
Neomercazole are equally safe from 2 nd trimester
onwards. Use minimum dose and keep the free T4 at
the upper limit of normal to prevent neonatal goiter.
Use of radionuclide imaging and radioiodine therapy
are absolutely contraindicated during pregnancy and
lactation.
Box 4. Approach to Thyroid Nodule
Endocrinology 131
Problem: Clinically apparent nodules are seen in 10%
of population and Ultrasonography based screening
methods increase this to 30 – 40%.
Risk factors for malignancy: Onset at extremes of
age, male sex, rapid growth, past history of radiation,
painful, certain sonographic features like 1
microcalcifications, increased nodular vascularity.
Management: Evaluation includes thyroid function
tests, Ultrasonography and FNAC of the thyroid.
Radionuclide uptake scan is suggested in cases with
low TSH only. No role for levothyroxine as
MEDICINE AND ALLIED
suppressive therapy for nodule / goiter.
Box 5. Emergencies in Thyroid
Myxedema Coma
Presentation: Clinical features include reduced level
of consciousness, seizures, hypothyroidism
hypothermia and a history of treated hypothyroidism
with poor compliance.
Clinical Setting: Always occurs in the elderly and is
usually precipitated by drugs (sedatives, anesthetics,
antidepressants), pneumonia, congestive heart failure,
myocardial infarction, gastrointestinal bleeding, or
cerebrovascular accidents, infection and sepsis, cold
exposure.
Management: Levothyroxine is administered via
nasogastric tube at a dose of 500 µg, which serves as a
loading dose. Further levothyroxine is given at a dose
of 50–100µg/d. Supportive therapy includes
correction of associated metabolic disturbances,
external warming, hydrocortisone (50 mg every 6 h),
broad-spectrum antibiotics and ventilatory support.
Thyrotoxic crisis
Presentation: Thyroid storm is characterized by fever,
delirium, seizures, coma, vomiting, diarrhea, and
jaundice. It is precipitated by acute illness, surgery on
the thyroid, or radioiodine treatment of an untreated
patient.
Management: Propylthiouracil (600 mg loading dose
and 200–300 mg every 6 h) should be given orally or
by nasogastric tube or per rectum. Stable iodide is
given one hour after the first dose of propylthiouracil.
Propranolol is given to reduce tachycardia and other
adrenergic manifestations (40–60 mg orally every 4 h;
or 2 mg intravenously every 4 h). Additional
therapeutic measures include glucocorticoids,
antibiotics, cooling, oxygen, and IV fluids.
 132 Textbook of Family Medicine
Chapter 3
OBESITY
1 Jaya Bajaj
Obesity has become a global epidemic and is not just a
problem of developed countries anymore. Obesity and
overweight are primary cause of many lifestyle diseases
MEDICINE AND ALLIED
as well as contribute towards certain cancers. Obesity
can be curbed by timely intervention of physicians.
Family physicians can play a crucial role in prevention of
obesity because they are usually the first point of contact
for patients.
Definition:
Obesity is a chronic medical condition in which excess
body fat is accumulated that may have adverse effect on
health. World Health Organization (WHO) uses body
mass index (BMI) to classify overweight and obesity.
BMI is defined as body weight in kilograms divided by
height in metres, squared. As a physician, one has to
understand that BMI does not differentiate between the
body weight due to fat or muscle. Also, there has been
significant research to modify the BMI cut-offs for Asian
population since Asians tend to develop negative health
consequences at lower BMI. See Table 1.
Epidemiology
The prevalence of obesity and overweight in India is
2.2% and 10% according to 1998 National Family Health
Survey. However, the above statistics are based on WHO
International BMI classification. Using the Asian cut-offs
the numbers are estimated to be higher. Moreover there
is rise in the numbers especially in urban, higher
socioeconomic conditions and in women.
Pathophysiology
Simplistically, obesity is a result of either increasing
calorie intake or decreasing energy expenditure or a
combination of both. However, there are number of
factors that can contribute towards obesity. Although
most cases of overweight and obesity are independent of
underlying medical conditions, a small number of cases
could be due to underlying medical condition or
medications taken for certain conditions.
Evaluation by Family Physician
Family physicians could see obese and overweight
patients for ailments unrelated to their weight.
Sometimes, these patients may present with symptoms
like joint pains, skin problems, daytime sleepiness,
fatigue or may come in to seek help with weight loss. A
detailed personal medical history including medication
history, social and family history could not just help
identify causes of obesity but may also help provide
information on the interventions that may work in
preventing obesity. By the time patients present with
elevated blood pressure, impaired glucose tolerance and
elevated cholesterol, lot of valuable time is already lost
and may need more aggressive interventions. A detailed
personal history should include the age of onset of
weight gain, nutritional history, physical activity, any
previous attempts at losing weight, and assessing
readiness to working on weight loss interventions. A
detailed questioning on review of symptoms like fatigue,
hair/skin changes, appetite disturbances, edema,
headaches, polyuria, polydipsia, joint pains etc should be
included. Any history of alcohol use, smoking or use of
illicit drugs should be asked in a non-judgmental manner.
Medication history should include prescription, over-the-
counter/herbal medications, and vitamin and mineral
supplements. Family history of obesity and
endocrine/metabolic should be obtained. See Table 3 for
physical exam and lab evaluation of obesity.
Management
Prevention is the key to success in preventing obesity.
The management of obesity and overweight is not just
losing weight but also being able to maintain weight in
normal range over long term. Readiness to lose weight,
and barriers and support systems play a huge role in
successful management of obesity. There are several
management options that are well researched across the
globe. Some of these therapies may, however, be outside
the scope of family medicine or require collaboration
with specialists (bariatric surgeons). Following steps may
be used as a basic infrastructure for management of
overweight and obese patients.
1. Assess the risk: Based on the BMI it can be
determined whether patient is at low, moderate or high
risk. The risk is magnified especially if patient already
has co-morbid conditions and higher waist
circumference. (See Table 3)
2. Assess Readiness to change, support system and
barriers: Since Obesity is a chronic condition and
requires lifestyle changes irrespective of any other
therapy regimen, it is important to assess patient’s
motivation level. The likelihood of success is also higher
if patient has a good support system- supportive family,
conducive work environment etc. Understanding barriers
may help family physicians to provide realistic
recommendations to the patients.
 Endocrinology 133

3. Determining the urgency of treatment: Patients at Table 2 Causes of Obesity

high risk with co-morbidities as a consequence of obesity
Causes of Obesity
may need to be treated more aggressively. Depending on
Primary Excessive caloric intake
their age and other risk factors, appropriate therapy can
1
Diet (E.g. skipping meals, binging, fast foods, composition)
be recommended.
Decreased physical inactivity
4. Choosing Treatment option: For low risk patients,
Genetic factors (MC4R gene mutation)
for example, young overweight or obese patients without
any significant risk factors may benefit from lifestyle Environmental factors (e.g. decreased access to
fruits/vegetables)
changes. A weight loss of 10% of body weight over 6
Secondary Mental illness (e.g Depression/Eating disorders)
months is recommended.
Drugs (steroids, antipsychotics, beta-blockers etc)
a. Dietary Therapy: Patient’s dietary preferences should

MEDICINE AND ALLIED

Endocrine/Metabolic (e.g hypothyroidism/Cushing’s
be kept in account to provide least disruptive diet since
syndrome)
patient is more likely to switch back to his/her diet after
sometime. Increasing consumption of fruits and
Table 3 Evaluation by Family Physician
vegetables have also been found to be beneficial for
weight loss. It is more important for patient to be History - Patient’s concerns
educated about balanced diet, portion sizes and healthy - Detailed Diet History- food diary/log, any
substitutes in meals. changes in diet, Servings of fruits and vegetables
b. Physical Activity: The benefits of physical activity - Physical Activity- intensity, duration and
frequency
are manifold. It not just helps to keep weight under
- Weight gain history: Age at weight gain,
control but also reduces risk of heart disease. Care must previous weight loss attempts
be taken to prevent injury while prescribing physical - Any past medical or surgical problems
activity regimen to obese patients. A moderate physical - Medication History
activity for 30 mins a day, at least 5 days a week has - Social History: Living conditions,
been found very effective. Tobacco/alcohol/Illicit drug use,
c. Pharmacologic Therapy: Few medications are - Family History: Obesity, Diabetes
available for high risk patients. These medications can be Mellitus, Hypertension, Hypothyroidism etc
considered with caution in high risk patients who did not - Review of systems to tule out co-
morbidities or consequences of obesity
respond to diet and exercise for more than 6 months.
d. Bariatric Surgery: Surgery is an option for patients Physical - Height, Weight, BMI calculation
Exam - Waist circumference (Directly correlates
with severe obesity. Motivated patients with severe with abdominal fat) (Increased risk if >90
obesity and co-morbidities may be referred to bariatric cm(males) and >80cm(females) in South Asian)
surgeons for evaluation. - Blood Pressure, Pulse
- Skin/Hair: Coarseness, skin texture,
Conclusion
pigmentation
Family physicians’ role is pivotal in early recognition - HEENT; Vision changes, macroglossia
and management of obesity. Multiple complications and - Neck: Any thyromegaly
health care costs can be reduced by timely recognition of - Chest: Any bradycardia, rales, rhonchi
obesity. History regarding diet and physical activity - Abdomen: Any organomegaly, striae,
should be part of a patient’s assessment whenever bruits
possible. Education of patient and his family regarding - Extremities: Edema, delayed relaxation of
prevention of obesity is the key to curbing this epidemic ankle jerks
of obesity. Laboratory Labs should be directed at findings from history and
Evaluation physical exam. Common labs ordered by family
physician are--
Table 1 Classification of Overweight and Obesity - Thyroid Profile
BMI = Weight in kilograms/(Height in metres) - Fasting Lipid panel
Classification WHO WHO Asian Risk of co- - Fasting and post-prandial glucose
International (Proposed) morbidities - CBC
Underweight <18.5 <18.5 Low - Liver function tests (especially if
Normal Range 18.5-24.9 18.5-22.9 Average increased triglycerides or alcohol use)
Overweight ≥ 25.0 ≥ 23.0 Increased - BUN/Creatinine and Electrolytes (if
hypertensive/diabetic)
At Risk 25.0-29.9 23.0-24.9 Moderate
Obese I 29.9-34.9 25.0-29.9 Severe (high)
Obese II 35-39.9 >30 Severe (high)
Obese III >40 Very Severe(high)
WHO 1998 and 2000
 134 Textbook of Family Medicine
Chapter 4
CALCIUM METABOLISM
1 Kamal K Sawlani, S K Sharma
The total amount of calcium is about 2 percent of the
body weight. Most of it (99%) is in the bones. The
MEDICINE AND ALLIED
normal total serum calcium level is 9-10.5 mg/dL (2.2-
2.6 mmol/L). Half of this is present in free form (ionized
calcium) and the remainder is bound with proteins
mainly albumin. The total serum calcium level is low in
conditions in which hypoalbuminemia exists, however,
free calcium level is normal. The ionized calcium is
responsible for the physiological functions of the calcium
such as nerve function and muscle contraction.
The calcium metabolism is regulated chiefly by the
parathyroid hormone (parathormone) and vitamin D.
Serum calcium level is principal regulator of parathyroid
hormone release. Parathyroid hormone maintains serum
calcium level by the following mechanisms;
a. It promotes resorption of calcium from renal tubules
b. It stimulates the synthesis of 1, 25-dihydroxy-
cholecalciferol by the kidneys and thus indirectly
promotes the absorption of calcium from the
intestine.
c. It promotes resorption of calcium from bones
Vitamin D enhances the absorption of calcium and
phosphate from the gut.
HYPOCALCEMIA
Table 1: Causes of hypocalcemia
Chronic renal failure
Vitamin D deficiency
Decreased intake
Decreased exposure to sun light
Malabsorption
Decreased production of active forms
Hypoparathyroidism
Pseudohypoparathyroidism
Multiple blood transfusions
Hyperphosphatemia
Hypomagnesemia
Acute pancreatitis
Low serum albumin (free calcium is normal)
Manifestations
Triad of manifestations of hypocalcemia is carpopedal
spasm, convulsions and laryngeal spasm. Other features
are muscle spasm, perioral and limb parasthesia. In
carpopedal spasm, there is flexion of
metacarpophalangeal joints, extension of interphalangeal
joints of fingers and thumb and apposition of thumb
(main d’ accoucheur).
Latent tetany can be detected by eliciting Trousseau’s
sign and Chvostek’s sign. Trousseau’s sign is the
appearance of carpal spasm within 3 minutes when
sphygmomanometer cuff on the upper arm is inflated
more than systolic blood pressure. Contraction of facial
muscles in response to tapping over the branches of
facial nerve as they emerge from the parotid gland is
called Chvostek’s sign.
The ECG may show prolongation of QT interval.
Arrhythmias may occur.
Prolonged hypocalcemia as in hypoparathyroidism may
cause cataract, basal ganglia calcification, raised
intracranial pressure, papilledema, and psychosis.
Investigations
Serum calcium is low. Serum phosphorus is elevated in
most of the causes of hypocalcemia except in vitamin D
deficiency where it is low. Serum parathyroid hormone
level is elevated except in hypoparathyroidism and
magnesium deficiency is given below. Serum magnesium
is measured to rule out hypomagnesemia.
Total serum calcium is normal but ionized calcium is low
in alkalosis. On the contrary, in hypoalbuminemia, total
serum calcium is low but ionized calcium is normal.
Treatment
Treatment of Severe Symptomatic Hypocalcemia
Calcium gluconate 2 g equivalent to 180 mg elemental
calcium (20 ml of 10% calcium gluconate intravenously
in 10-15 minutes) should be given. This should be
followed by infusion of 60 ml 10 percent calcium
gluconate in 500 ml dextrose water slowly in 4-6 hours.
Subsequently the infusion rate should be adjusted to
maintain serum calcium level between 8-9 mg/dl.
Magnesium should also be corrected if low.
 Endocrinology 135

The underlying cause should be treated and long term Sarcoidosis, Vitamin D excess
therapy started. Hyperthyroidism, Lithium and thiazide use
Milk alkali syndrome, Immobilization
Long-term Treatment
Table 4: Clinical Features of Hypercalcemia
Oral calcium supplement is given in the dosage of 1-2
gm elemental calcium daily. The preferred salt is calcium
The symptoms generally occur if serum calcium level is
more than 12 mg/dL.
1
carbonate which is the least expensive and is well Gastrointestinal
Anorexia
tolerated. The calcium when given with food is well
Nausea
absorbed. The goal is to maintain serum calcium level Vomiting
between 8-8.5 mg/dl. At this level, the symptoms of Peptic ulcer

MEDICINE AND ALLIED

hypocalcemia are avoided and the chance of Constipation
hypercalciuria is minimal. Renal
Polyuria
The vitamin D is supplemented in the dosage of 400- Polydipsia
1000 units per day. The dose of active form of vitamin D Renal colic
Nephrolithiasis
(1, 25- dihydroxycholecalciferol, calcitriol) is 0.25-0.5 Neurological
µg daily. Confusion
Depression
Table 2: Laboratory findings in hypocalcemia Drowsiness
Stupor and coma
ECG findings include short QT interval and
ventricular arrhythmias

HYPERCALCEMIA
Primary hyperparathyroidism and malignancy account
for 90 percent of all the case of hypercalcemia.
Hypercalcemia in tumors may occur due to (a) metastasis
in bone (b) increased bone resorption due to increased
osteoclast activating factor (OAF), and (c) production of
PTH related peptide (PTHrP). Sarcoidosis may cause
hypercalcemia by increased production of vitamin D 3 by
granulomatous tissue. Increased bone turn over in
hyperthyroidism may lead to hypercalcemia. Prolonged
immobilization may cause hypercalcemia due to
continuing bone resorption in the absence of normal
postural stimuli for bone formation. Milk alkali
syndrome is due to ingestion of large amount of calcium
and absorbable antacids such as milk or calcium
carbonate.
Table 3: Important causes of hypercalcemia
Primary hyperparathyroidism
Adenoma, Hyperplasia, Carcinoma
Malignancy
Tumors producing PTH related proteins (malignancy of
lung, ovary, kidney)
Hematological malignancies (Myeloma, lymphoma,
leukemia)
Other causes
Investigations
Serum calcium and serum PTH levels are measured.
High PTH level is present in primary hyperpara-
thyroidism while it is low in malignancies where
parathyroid related protein (PTHrP) is raised. Other tests
are done to detect the presence of malignancies if
suspected. Measurement of thyroid hormones and
vitamin D levels may be required.
Treatment
a. Saline diuresis is induced by giving an infusion of
saline which promotes the excretion of calcium.
Frusemide may be added in case of renal impairment
or heart failure.
b. Bisphosphonate (60-90 mg pamidronate or
zoledronate 4 mg) is given intravenously. It inhibits
bone resorption. This is the drug of choice in
malignancies.
c. Restoration of extracellular fluid volume is done with
0.9 percent saline. Three to four liters of fluid may be
needed in the first 24 hours.
d. Calcitonin (IM or SC) may be given particularly
when there is renal failure. It inhibits bone resorption
and promotes calcium excretion.
e. Oral glucocorticoids are effective in hypercalcemia
due to hematological malignancies, sarcoidosis and
vitamin D toxicosis.
f. Hemodialysis may be needed in cases of renal failure
and heart failure.
 136 Textbook of Family Medicine

g. The underlying cause should be treated. Para-

thyroidectomy is done in primary hyperthyroidism.

1
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